Anticancer agents effect tumor cell killing both in vivo and in vitro through the induction of apoptosis. Endonuclease-mediated internucleosomal DNA fragmentation, the most widely used biochemical marker of apoptosis, has been shown to play a central role in apoptosis in many experimental systems. In the present investigation, we report that activation of endonuclease(s) leading to oligonucleosomal DNA fragmentation is common and an essential event in apoptosis, induced by different anticancer drugs, adriamycin, etoposide and cisplatin. The endonuclease inhibitors aurintricarboxylic acid and zinc ion prevented apoptotic cell death in human monocytic leukemic cell line U937, as documented by DNA fragmentation, morphological and nuclear alterations, and cell viability assay. Additional studies suggest endonuclease(s)-mediated DNA fragmentation may not play a central role in apoptosis in the same cell line in response to other inducers such as heat shock and cells may undergo cell death showing all morphological features of apoptosis even in the absence of DNA fragmentation.