An early clinical trial of pentamethylmelamine (PMM) the monodemethylated derivative of hexamethylmelamine, was conducted in 22 adults with solid tumors. PMM was administered as a 2-hour iv infusion every 4 weeks at doses ranging from 40 to 2400 mg/m2. A combination of gastrointestinal and neurologic (CNS) toxicity was dose-limiting. Nausea and vomiting began at a dose of 265 mg/m2 and became progressively worse until it became life-threatening at doses of 1800-2400 mg/m2. CNS toxic effects consisting of agitation, confusion, drowsiness, and loss of consciousness were first noted at a dose of 1200 mg/m2 and were seen in varying degrees at all higher dose levels. No other toxic effects were noteworthy except two instances of thrombocytopenia at low doses. No antitumor activity was observed. We do not recommend the further use of this schedule of administration for PMM.