Phase II studies utilizing VP-16 in the treatment of 58 patients with malignant lymphoma and 48 patients with acute leukemia were carried out. Most of the patients entered had received prior chemotherapy. The initial dose of VP-16 administered was 60∼100 mg/m2 by iv infusion on days 1∼5 every 3 weeks.In malignant lymphoma, objective responses were seen in two of 6 (33.3%) patients with Hodgkin's disease (two PR) and in 19 of 40 (47.5%) patients with non-Hodgkin's lymphomas (seven CR, twelve PR). By tumor type, in non-Hodgkin's lymphoma the best responses were obtained in diffuse mixed and large cell types (LSG classification).In acute leukemia, no responses were noted in 4 patients with ALL, while an overall response rate of 37.9% was achieved (6.9% CR, 31.0% PR) in AML. The best responses were obtained in monocytic type including M4 and M5 according to FAB diagnosis. On the other hand, cytoreduction by VP-16 infusion was seen in all of the FAB subtypes.The dose limiting toxicity was hematological. Alopecia and gastrointestinal toxicity were highly frequent side effects, but which were well tolerated. It is concluded that VP-16 administered iv has significant activity particularly in diffuse mixed and large cell types of malignant lymphoma and in monocytic type of AML. Its use in drug combinations should now be assessed.