The Caenorhabditis elegans gene ced-9 and the human proto-oncogene bcl-2, both of which protect cells from programmed cell death, are members of the same gene family. ced-9 and bcl-2 were discovered because of the effects of dominant gain-of-function mutations. Such bcl-2 mutations, which are commonly found in follicular lymphoma, are translocations that result in over-expression of a normal Bcl-2 protein in B cells. Here we report that, by contrast, the ced-9(n1950) gain-of-function mutation affects the open reading frame of ced-9 and results in a glycine-to-glutamate substitution in a region highly conserved among all ced-9/bcl-2 family members. We conclude that this glycine has an important function in ced-9 regulation, and we suggest that alteration of this glycine in other members of the ced-9/bcl-2 family might lead to oncogenic activation. We also present genetic evidence suggesting that the CED-9 protein might exist in two distinct forms that have opposite effects on cell death.