Residual leukemic cells in a bone marrow graft may increase the risk of relapse after autotransplantation. We have compared the efficacy of etoposide with that of mafosfamide, which has been used mainly for purging in acute leukemias. First, we examined the effects of VP-16 and ASTA-Z on the normal hematopoietic progenitors and on the erythroleukemic cell K562. Subsequently, we evaluated purging activity in cocultures using two different ratios of leukemic contamination. The most effective drug concentrations in inhibiting 100% of K562 growth were 50 micrograms/ml of ASTA-Z and 70 micrograms of VP-16. Residual growth of normal colony-forming units-granulocyte-macrophage (CFU-GM) was 4.8% with VP-16 and 32.5% with ASTA-Z. In treated cocultures, ASTA-Z produced a higher inhibition of the K562 line than VP-16 at both levels of leukemic cell contamination. At 0.5% contamination, VP-16 showed higher toxicity toward normal hematopoietic progenitors than ASTA-Z. At the 5% contamination level, VP-16 completely inhibited colony formation, whereas ASTA-Z spared some normal progenitor cells (21.2%). In conclusion, in our experimental model, VP-16 did not show improved efficacy over ASTA-Z in killing leukemic cells and in sparing normal progenitors.