We have found that the alkyl-lysophospholipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) was able to induce apoptosis in human promyelocytic HL-60 leukemic cells, as evidenced by the internucleosomal degradation of the cellular DNA into the characteristic 180-200 bp DNA fragments. This effect was observed after short periods of cell incubation (6 h) with low doses of ET-18-OCH3 (3 micrograms/ml). Furthermore, we found that ET-18-OCH3 also induced rapidly apoptosis in human promonocytic U937 leukemic cells. In contrast, 3T3 fibroblasts were resistant to the alkyl-lysophospholipid. ET-18-OCH3 induced apoptotic cell death of tumor epithelial-like HELA cells, but this process required prolonged times of incubation. These data demonstrate that ET-18-OCH3 promotes a rapid and selective programmed cell death in human leukemic cells, providing an explanation to the previously described cytotoxic effects of this compound on leukemic cells.