A phase I study of benzisoquinolinedione (amonafide) was conducted in 30 patients with advanced solid tumors refractory to conventional therapy. The starting dose was 10 mg/m2/day X 5 days and the highest tolerated dose was 625 mg/m2/day X 5. The daily dose was mixed in 100 ml of normal saline and infused over 30-60 minutes. The dose-limiting toxicity was myelosuppression with nadirs of blood counts reached on Day 15 and recovery by Day 21-28. Other side effects included mild nausea and vomiting, mild phlebitis, skin rashes, and alopecia in some patients. A majority of the patients experienced dizziness, tinnitus, and hot flushes occurring predominantly at the higher dose levels. These were related to the rate of drug infusion and resolved on prolonging the infusion to 60 minutes. Pharmacokinetic studies of amonafide revealed a monoexponential plasma disappearance curve with a mean half-life of 3.5 +/- 1.9 hours. The recommended dose of amonafide for phase II studies in solid tumors is 400 mg/m2/day X 5 for good-risk and 300-320 mg/m2/day X 5 days for poor-risk patients with courses repeated at 21-28-day intervals.