The black-footed ferret, North America's rarest mammal, is returning to the western prairie 35 years after being declared extinct.

The comeback trail for Mustela nigripes began in 1981, when a ranch dog with a dead ferret in its mouth led to the rediscovery of a remnant population near Meeteetse in northwestern Wyoming. (See stunning pictures of the rarest animals on Earth.)

The last 18 survivors of that population formed the seed stock for a captive-breeding program that reintroduced the species to its former range at 25 sites from southernmost Canada to northern Mexico. Yet numbers in the wild remain low—fewer than 500, according to Peter Gober, recovery coordinator at the U.S. Fish and Wildlife Service's National Black-Footed Ferret Conservation Center in Carr, Colorado.

A major hurdle is disease, particularly sylvatic plague, a flea-borne infection that appeared in North America in the early 1900s. Because the disease is non-native, the black-footed ferret—a member of the weasel family—has no natural resistance; neither does its prey, the prairie dog. (Related: [Video] "Why Do Prairie Dogs Do 'The Wave'?")

Prairie dogs are "pretty much all the ferrets eat," Gober says. They also "provide shelter, because the ferrets make use of their burrows.

"There are quite a few prairie dogs in the West still, despite the fact that they've been reduced by 90 percent plus since historical times," he adds. "The problem is that they fluctuate wildly, due to drought and because of this plague."

The reintroduced ferret populations mirror these fluctuations. They "come and go" like "lights blinking on a Christmas tree," Gober says. (Read about how scientists decide what species to save.)

Repopulating ferrets over a wide range of their old territory helps manage the risk of disease, but that requires access to suitable land with plenty of prairie dogs. "There's a lot of raw habitat out there, but it's degraded," Gober says. Such habitat is typically found on livestock ranches, where historically prairie dogs haven't been welcome. Because they compete with cattle for grass, millions were exterminated during the past century.

Wealthy landowners like media mogul Ted Turner are already on board with the program, but accommodating the ferrets' increasing need for habitat will require financial support for the ranching community in return for tolerating significant numbers of prairie dogs.

The Natural Resources Conservation Service, a division of the U.S. Department of Agriculture, so far has provided about a million dollars to a dozen landowners in Colorado, and hopes to expand the program to other states.

New hope also comes in the form of a recently developed vaccine to combat sylvatic plague.

Meanwhile, Gober and his colleagues in Colorado are breeding some 250 black-footed ferrets annually.