We studied factors associated with occurrence of high-amplitude population fluctuations of the prairie vole (Microtus ochrogaster) in alfalfa, bluegrass, and tallgrass habitats in east-central Illinois for 25 years. Increased survival was the most important factor associated with initiation of a population fluctuation during a given year. The proportion of reproductively active adult females was not associated with initiation of population fluctuations. The interval between fluctuations was not correlated with the previous peak density. We propose that population fluctuations in M. ochrogaster were initiated by the net effects of relaxation of predation pressure of multiple generalist predators, which occurred erratically across years.