Human promyelomonocytic leukemia cells HL-60 were treated with etoposide or cytochalasin B to induce apoptosis or necrosis, respectively. We report here that during necrosis, the DNA-repair associated nuclear enzyme poly(ADP-ribose) polymerase (PARP) was degraded differently from that observed during apoptosis. While apoptotic HL-60 cells exhibit only the signature 89 kDa fragment of PARP, necrosis of these cells was accompanied by formation of major fragments at MWr approximately 89 and 50 kDa and minor fragments at approximately 40 and 35 kDa. The necrosis-specific degradation of PARP was coincident with other changes detected by flow cytometric analysis, but earlier than the extensive degradation of DNA. Therefore, the unique necrotic degradation of PARP could be used as a sensitive indicator for necrotic death of cells.