A fundamental assumption underlying the application of genetics within conservation biology is that inbreeding increases the risk of extinction. However, there is no information on the shape of the relationship, the available evidence has not distinguished genetic and nongenetic effects, and the issue is controversial. Methods were devised to separate genetic and nongenetic causes of extinction in inbred populations, and they were used to analyze data from Drosophila melanogaster, D. virilis and Mus musculus. Inbreeding markedly increased rates of extinction in all cases. All showed a threshold relationship between incremental extinction and inbreeding with low initial extinction, but they showed notably increased extinction beginning at intermediate levels of inbreeding. There was no difference in extinction levels at similar inbreeding coefficients in populations inbred at different rates (full sibling versus double first cousin). Endangered species may give little warning of impending extinction crises due to inbreeding.