But Mr. Rey said that to not deal with prairie dogs could hurt the program. “Prairie dogs are spreading off federal land to private land,” he said. “And our goal is to keep the black-footed ferret program with broad public support, and one way to do that is to make sure prairie dogs don’t spread onto private land.”

Black-tailed prairie dogs, food for numerous prairie predators, may be threatened themselves. A few years ago the Fish and Wildlife Service, in response to a petition, decided they were warranted for listing as a protected species, but precluded because of higher priorities. That designation was later changed and is now being reconsidered.

For now, though, efforts are focused on stopping the disease.

Losing this population to the plague would be a blow for the entire ferret recovery program and personally heartbreaking, said Mr. Livieri, who has worked for 13 years to restore this population south of Badlands National Park. He started with the National Park Service, then worked for the Forest Service and now cobbles together financing for his own nonprofit organization, Prairie Wildlife Research.

Until now this was the most robust population of ferrets, so healthy it provided wild kits for other recovery efforts in Colorado, Montana, Utah, Mexico and elsewhere. “Last year 52 ferrets came out of here to supplement or start new populations,” Mr. Livieri said.

Most of those populations have struggled with plague and other problems. One population, near Shirley Basin, Wyo.  where the 18 surviving ferrets were found  has struggled with plague but now may have close to the number of ferrets here. There are thought to be about 1,300 ferrets extant, 1,000 or so in the wild and 300 in captivity.

Plague thrives in wet years, and this has been one of the wettest in the region in years. A combination of insecticide and vaccines can be very effective, said Dr. Dean Biggins, a research biologist with the United States Geological Survey, who has studied plague and ferrets. He said he had seen a plague outbreak hit a line of dusted burrows and stop cold. “There’s no question they can be protected,” he said. “It’s not whether we can do it, but are we willing because of cost and labor? It might have to be done every year or two.”

For now, the race is on to protect the heart of the ferret population. Mr. Livieri, often working by himself, drives from his home in Wellington, Colo., six hours away, and spends a week or two at a time scouring the prairie all night in hopes of injecting all of the ferrets.