A phase II study of VP-16, a semisynthetic Podophyllotoxin, was performed in patients with solid tumors. VP-16 was administered orally at a dose of 200mg/day for 5 consecutive days at 3 to 4-week intervals. Out of 41 patients who were entered into the study, 35 patients comprising 17 lung cancer, 10 hepatoma and 8 other tumors were evaluable. There were 4 partial responses (23.5%) for lung cancer, 1 (10.0%) for hepatoma and 1 for rhabdomyosarcoma. Overall response rate was 18.2% for patients with prior chemotherapy and 15.4% for those given no prior chemotherapy respectively. Thus the results indicated VP-16 has no cross-resistance to other antitumor agents. Leukopenia (less than 4,000/mm3) and thrombocytopenia (less than 10 X 10(4)/mm3) were observed in 72.7% and 29.4% of the patients, respectively. Other toxicities were alopecia (59.5%) and gastrointestinal disturbances such as nausea (46.2%), vomiting (20.5%) and anorexia (20.5%), but these were all well tolerated.