(CNN) The deadliest terrorist attack on U.S. soil since 9/11 followed a clarion call by ISIS to its supporters in the United States to launch attacks during Ramadan, the Islamic Holy Month, which started last week.

In an audio recording released on May 21, ISIS spokesman Abu Mohammed al Adnani called for "a month of hurt" in the United States as well as Europe.

His message to ISIS sympathizers like Orlando shooter Omar Mateen : Stay home and kill anybody, anyhow, anywhere.

'Terrorize them'

"The smallest action you do in the heart of their land is dearer to us than the largest action by us, and more effective and more damaging to them," al Adnani said, according to a translation by the SITE Intelligence Group.

"And if one of you wishes and tries hard to reach the Islamic State, then one of us wishes to be in your place to hurt the Crusaders day and night without sleeping, and terrorize them so that the neighbor fears his neighbor."

It was the latest in a series of calls for attacks by Adnani, whose fatwas describing hitting the West as religious duty have motivated multiple plotters on both sides of the Atlantic to launch attacks.

It was also the most strident call for attacks yet and a sign ISIS is mobilizing its supporters and fighters to wage an all-out campaign of revenge as it loses territory in Syria, Iraq and Libya.

Western intelligence officials believe Adnani oversees ISIS' external attack plotting and had command responsibility for the Paris and Brussels attacks.

Photos: Orlando nightclub shooting Police investigate the back of the Pulse nightclub in Orlando on Sunday, June 12. At least 49 people were killed there by Omar Mateen, who was shot and killed by Orlando police. It was the deadliest mass shooting in U.S. history. Hide Caption 1 of 20 Photos: Orlando nightclub shooting Bodies arrive at the medical examiner's office on June 12. Hide Caption 2 of 20 Photos: Orlando nightclub shooting Friends and family react after a list of hospitalized victims is released June 12 outside a hotel near the Orlando Regional Medical Center. Hide Caption 3 of 20 Photos: Orlando nightclub shooting Pastor Kelvin Cobaris embraces Orlando City Commissioner Patty Sheehan, right, and Terry DeCarlo, executive director of the LGBT Center of Central Florida, on June 12. Hide Caption 4 of 20 Photos: Orlando nightclub shooting Jeremy Glatstein donates blood in Orlando on June 12. He drove an hour to the donation center to show his support for the shooting victims. Hide Caption 5 of 20 Photos: Orlando nightclub shooting A bomb disposal unit checks for explosives around the apartment building where Mateen is believed to have lived in Fort Pierce, Florida. Hide Caption 6 of 20 Photos: Orlando nightclub shooting Ray Rivera, a DJ at the nightclub, is consoled by a friend outside of the Orlando Police Department. Hide Caption 7 of 20 Photos: Orlando nightclub shooting Florida Gov. Rick Scott arrives at the scene. Hide Caption 8 of 20 Photos: Orlando nightclub shooting Police gather outside the home in Port St. Lucie, Florida, where Mateen's father lives. Hide Caption 9 of 20 Photos: Orlando nightclub shooting Police officers gather outside of the nightclub, which describes itself as "the hottest gay bar" in the heart of Orlando. Hide Caption 10 of 20 Photos: Orlando nightclub shooting Ron Hopper of the FBI answers questions from members of the media on June 12. Listening are Orlando Police Chief John Mina, left, and Orange County Mayor Teresa Jacobs. Hide Caption 11 of 20 Photos: Orlando nightclub shooting A police officer stands guard outside the Orlando Regional Medical Center. Hide Caption 12 of 20 Photos: Orlando nightclub shooting A SWAT team member arrives at the scene of the shooting. Hide Caption 13 of 20 Photos: Orlando nightclub shooting Medical personnel wait with stretchers at the Orlando Regional Medical Center. Hide Caption 14 of 20 Photos: Orlando nightclub shooting People wait for news outside the emergency entrance of the hospital. Hide Caption 15 of 20 Photos: Orlando nightclub shooting Police in Orlando direct family members away from the scene of the shooting. Hide Caption 16 of 20 Photos: Orlando nightclub shooting Shooting victims are attended to by emergency responders outside the club. Hide Caption 17 of 20 Photos: Orlando nightclub shooting Emergency personnel gather outside the nightclub. Hide Caption 18 of 20 Photos: Orlando nightclub shooting Bystanders wait at the scene. Hide Caption 19 of 20 Photos: Orlando nightclub shooting Police officers respond to the scene of the shooting. Hide Caption 20 of 20

Loss of appeal?

The Orlando attack comes at a time when there are some signs ISIS is losing its appeal in the United States.

Last month, FBI Director James Comey said there had been a sharp drop in the number of Americans attempting to travel to Syria and Iraq to join ISIS.

In the first half of 2015, the FBI was seeing six to 10 American residents trying to travel each month, a figure that dropped to just one per month since August 2015. But one concern officials have had is that American ISIS sympathizers unable to reach the so-called caliphate would attempt to launch attacks in the United States instead.

In previous messages, ISIS has told its supporters they will be rewarded tenfold in paradise for carrying out attacks during Ramadan, an example of them inventing theological precepts to suit their purposes.

The group has also made clear its visceral and vicious homophobia by throwing people they suspect of being gay off buildings in their so-called caliphate and stoning them.

No direct ties

Orlando gunman Mateen swore allegiance to ISIS in a 911 call as his attack got underway, providing ISIS with an opportunity to claim ownership of the attack. Hours after the massacre, the ISIS-affiliated Amaq news agency claimed the attack had been carried out by an ISIS fighter, without offering any proof of advance knowledge.

As of Sunday night no evidence had emerged of direct organizational ties between Mateen and ISIS.

The emergence of ISIS has seen its message resonate in the United States over the past two years, partly because it has so skillfully exploited social media to spread its propaganda and create a virtual community of like-minded followers who constantly interact and reinforce each other.

According to a database maintained by the majority staff of the House Homeland Security Committee, U.S. law enforcement agencies have 1,000 active investigations into U.S. homegrown jihadis, 80% of which involved ISIS sympathizers.

Since 2014 there have been 87 sympathizers charged with terror-related offences in the United State and there have been 25 terrorist plots inspired by or instigated by ISIS. Many of those were thwarted in FBI sting operations.

Under the radar

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The high number of cases is likely one of the reasons Mateen was not under surveillance at the time of the attacks.

With investigations in 50 states, U.S. law enforcement agencies have had to prioritize. Mateen first came across the FBI radar screen in 2013 after co-workers flagged signs of radicalization.

In 2014, the FBI interviewed Mateen again over possible connections with a fellow Floridian, Moner Mohammad Abu-Salha , who joined al Qaeda in Syria and blew himself up in a suicide truck bombing in May that year.

In a video recorded before his death, Salha stated he had attempted to recruit Florida friends to travel with him to Syria. The FBI found no grounds for continuing its investigation of Mateen.

"We determined that contact was minimal and did not constitute a substantive relationship or threat at that time," said FBI Assistant Special Agent in Charge Ronald Hopper.

Few but deadly

American Muslim leaders were swift to condemn the Orlando shootings. The overwhelming majority of American Muslims reject ISIS' ideology, with radicalization rates being far lower in the United States than in European countries like France or the United Kingdom.

But a key and growing concern of U.S. counterterrorism officials is that ISIS operatives in Syria and Iraq are communicating directly with American sympathizers by using online encryption messaging apps, grooming them for attacks.

On the morning of an attack at a "Draw the Prophet Mohammed Contest" in Garland, Texas, in May 2015, British ISIS operative Junaid Hussain exchanged 109 messages with one of the gunmen.

"In the course of the period from April 1 to July 4 in New York City, and from Boston to Morgantown, North Carolina, we had a dozen arrests in three or four plots, two of which targeted New York City directly, and this was all based on ISIS meeting people on Twitter and talking to them on encrypted apps," NYPD counterterrorism Commissioner John Miller told CTC Sentinel earlier this year.

"What we were seeing was a pace of cases and arrests and plotters that we hadn't seen before. We were seeing that the mass marketing of terrorism was starting to be more effective than we had ever seen with any other kind of messaging before."

Another longstanding concern of U.S. counterterrorism officials is the relatively easy access to powerful weapons in the United States.

There have been a string of deadly Islamist terrorist attacks involving firearms in the United States, including the killing of five members of the U.S. military in July 2015 in Chattanooga, Tennessee, and 14 people at a holiday party last December in San Bernardino, California , an attack also inspired by ISIS.

In 2011 al Qaeda instructed its followers to take advantage of what by international standards are weak gun laws.

While terrorist groups don't have nearly as many supporters in the United States, it's much easier for followers of such groups to get guns.