Venoms are rich source of several bioactive compounds that possess therapeutic potentials. The different constituents of scorpion venom can modulate cell proliferation, cell growth and cell cycle. In the present communication, the cytotoxic activity of Indian black scorpion (Heterometrus bengalensis) venom was explored on human leukemic U937 and K562 cells. Scorpion venom induced U937 and K562 cell growth inhibition and the IC50 value calculated to be 41.5 μg/ml (U937) and 88.3 μg/ml (K562). The scorpion venom showed characteristic features of apoptosis such as membrane blebbing, chromatin condensation and DNA degradation in both the cells as evidenced by confocal, fluorescence, scanning electron microscopy. Scorpion venom (IC50 dose, 48 h) induced DNA fragmentation as evidenced by comet formation. Flow-cytometric assay revealed a significant amount of apoptotic cells (early and late) due to scorpion venom treatment. The venom induced cell cycle arrest was observed with maximum cell accumulation at sub-G1 phase. Thus, the Indian scorpion (H. bengalensis) venom possessed antiproliferative, cytotoxic and apoptogenic activity against human leukemic cells. © 2006 Elsevier Ltd. All rights reserved.