Numbers of lions in the Ngorongoro Crater have been knocked severely by several bouts of acute disease over the past 40 years.
The Ngorongoro Crater in Tanzania is a truly unique place
Between 1994 and 2001, outbreaks of canine distemper virus have kept the lion population low, with numbers dipping to just 29 individuals in 1998.
The scientists suggest that climate change, or an increasing local human population could be to blame.
The research is detailed in the Proceedings of the Royal Society B.
The Ngorongoro Crater in Tanzania is a truly unique place. The crater, which is 610m deep and 260km squared, is a microcosm of East African scenery and wildlife.
Many crater animals, like lions, live there and there alone, making it a near-contained mini biosphere.
For scientists that is very interesting, because it is easier for them to know exactly what pressures the creatures face. They can follow a population of animals over time, and record how changes in things like food supply, or competition, affect them.
The lions of the Ngorongoro Crater have been monitored closely since the 1960s. One question researchers wanted to answer was what regulated their population numbers.
In large carnivores like lions, one might expect food supply to be the main limiting factor. But in recent years, disease is a more likely restriction, according to Bernard Kissui and Craig Packer, of the University Minnesota, US.
There are probably enough prey animals like buffalo in the Ngorongoro Crater to support about 120 lions.
But at various times over the last 40 years lion numbers have dropped well below that - and in the last 10 years there have rarely been more than 60 in the crater.
Kissui and Packer believe that disease is the biggest culprit in this population dip.
In 1962, the crater lion population crashed from about 100 to 12, which coincided with an outbreak of blood-sucking stable flies.
After this severe knock, the population climbed again, to reach over 100 by 1975. Lion numbers then simmered away at fairly stable proportions until 1983, when they went into decline again - reaching a low point of 29 individuals in 1998.
The Ngorongoro Crater contains a wealth of wildlife
"Disease appears to be the only factor that has held the crater lion population below its carrying capacity for the past 10 years," Bernard Kissui and Craig Packer write in their research paper.
Although many diseases threaten lions, canine distemper virus (CDV), which normally affects dogs, has been a particular menace to the big cats.
The researchers are not entirely sure what has caused this increase in levels of disease.
They suggest it could be due to the fact that there are many more humans in the area now, and with them come domestic dogs - which carry CDV.
Or disease outbreaks could be exacerbated by climate change. In the last 10 years East Africa has suffered many more droughts and floods, which seem to coincide with bouts of disease.
"The weather in East Africa was more variable in the 1990s than in the 1970s and 1980s, and all four lion die-offs coincided with drought and flood," write Kissui and Packer.
"The 1962 [stable fly] plague coincided with heavy floods that immediately followed a severe drought in 1961... and the 2001 CDV epidemic followed the drought of 2000."
Whatever the cause of the disease outbreaks, they put the fragile population of Ngorongoro Crater lions at serious risk.
Kissui and Packer concluded: "Endangered populations can remain at serious risk even with a large, stable food supply and no real threats from competing species."