The cytochalasins are fungal metabolites that have previously been shown to have some chemotherapeutic potential. When various cell types are treated in vitro with both cytochalasin B and vincristine, the resultant DNA fragmentation is greater than the sum of that caused by each agent alone. The levels necessary to achieve this potentiation are obtainable in vivo. DNA fragmentation induced by cytochalasin E, an actin-specific agent, is potentiated by vincristine. Pretreatment of the mastocytoma line P815 with vincristine results in an enhancement of the ability of cytochalasin B to fragment DNA. These results indicate that cytochalasin B might be effective as a chemotherapeutic agent in the presence of vincristine.