We have identified a Drosophila homolog of Apaf-1 and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent manner in vitro. During embryonic development, hac-1 is prominently expressed in regions where cells undergo natural death. Significantly, hac-1 transcription is also rapidly induced upon ionizing irradiation, similar to the proapoptotic gene reaper. Loss of hac-1 function causes reduced cell death, and reducing the dosage of hac-1 suppresses ectopic cell killing upon expression of the dcp-1 procaspase in the retina but has little effect on reaper, hid, and grim-mediated killing. Our data indicate that caspase activation and apoptosis in Drosophila are independently controlled by at least two distinct regulatory pathways that converge at the level of caspase activation.