N-Methylformamide (N-MF) belongs to a class of polar-planar compounds which induce cellular differentiation. Preclinical antitumor activity was demonstrated against human mammary, colon, and lung tumor xenografts and L1210 and P388 murine leukemias. This phase I study used a single bolus infusion of N-MF given weekly X 3 doses every 6 weeks. Thirty-five patients were treated with N-MF at doses which ranged from 125 to 3125 mg/m2/week. The dose-limiting toxic effects included nausea and vomiting, anorexia, malaise, and liver function abnormalities. No myelosuppression was seen. The recommended dose for phase II trials of N-MF with this schedule is to initiate therapy at 2000 mg/m2 weekly X 3 and escalate to 2500 mg/m2 if the initial dose was well tolerated.