A new semisynthetic podophyllotoxin derivative VP-16 has been evaluated in a phase II study on malignant lymphomas. The drug was administered orally by capsule at a dose of 100mg twice a day for 5 consecutive days at 3-4-week intervals to a total of 53 patients. Objective responses were noted in 9 patients (25%), 4 with CR and 5 with PR, out of 36 patients with non-Hodgkin's lymphoma, while none of 5 patients with Hodgkin's disease responded. Two of 5 patients with adult T-cell lymphoma attained a PR. Overall objective response rate was 24%. Dose-limiting toxicity was hematologic and alopecia was also observed. Gastrointestinal toxicity was moderate. These results demonstrated that VP-16 administered as an oral capsule is effective against malignant lymphomas and suggested a lack of clinical cross-resistance to standard chemotherapeutic agents.