Internucleosomal fragmentation of DNA, the most widely used biochemical indicator of apoptosis, is believed to contribute to loss of viability because the nuclease inhibitor, aurintricarboxylic acid, delays or prevents cell death in a range of experimental systems. We report here that auritricarboxylic acid inhibits topoisomerase II in vitro, the concentration required (< or = 0.2 microM) being less than that usually employed in studies of apoptosis. Since topoisomerase II mediates chromatin condensation during apoptosis, the efficacy of ATA in preventing or delaying cell death may not be the result of nuclease inhibition.