Treatment of L1210 cells with prostaglandin A2 (PGA2) or 9-deoxy-delta 9,12-13,14-dihydro PGD2 (delta 12-PGJ2) resulted in significant G2/M arrest and subsequent DNA fragmentation at concentrations that are cytotoxic to the cells. On agarose gel electrophoresis, DNA ladder formation was evident 24 h after the addition of delta 12-PGJ2 and remained apparent through 72 h, whereas G2/M accumulation was observed 6 h after the treatment. When the morphology of cells was examined by electron microscopy, L1210 cells incubated with a cytotoxic dose of PGA2 or delta 12-PGJ2 for 24 h showed the characteristic morphological features of apoptosis such as chromatin condensation, nuclear fragmentation and formation of apoptotic body. Cycloheximide blocked the DNA fragmentation and morphological changes induced by delta 12-PGJ2. Our results suggest that these cyclopentenone PGs caused apoptotic cell death of L1210 cells which is preceded by G2/M accumulation and requires de novo protein synthesis.