Thirty-nine adults with solid tumors were treated on a Phase I study of menogaril administered i.v. once each week. Granulocytopenia was dose-limiting at a menogaril dose of 115 mg/m2/wk. Ten patients required delays in treatment of 1-4 weeks (median, 1 week) at some point during their treatment until they recovered from granulocytopenia. The average dose intensity possible on this schedule was at least 80% higher than that possible using a single-day or a five-times-daily schedule every 4 weeks. One patient developed infection while neutropenic, and only one patient developed thrombocytopenia. Dexamethasone appeared to reduce the degree of myelosuppression. Gastrointestinal toxicity was quite mild, and alopecia was uncommon. Arm vein phlebitis frequently followed menogaril administration, requiring the use of Hickman catheters (or equivalents). Two patients had myocardial infarcts while on treatment. It was unclear if the menogaril was in any way responsible. Reversible dyspnea and cough (with no evidence of congestive heart failure) were seen in some patients. Responses were seen in patients with gliomas, renal-cell carcinoma, and bladder carcinoma, and marked subjective improvement occurred in a single patient with prostate cancer. We plan to conduct a Phase II study in astrocytoma patients using a menogaril dose of 115 mg/m2/wk i.v.