Two dose schedules of methyl CCNU were compared for drug effect and toxicity. One hundred thirteen patients were stratified by tumor site, performance status, and prior chemotherapy and randomized to 100 mg/m2 q 3 wk or 200 mg/m2 q 6 wk orally. Response rates were similar (12% vs. 18%, respectively, in the major tumor sub-types studied) and survival was equivalent. Hematologic toxicity, however, was significantly different, with earlier time to the most severe blood count depressions, more frequent occurrence of severe depression, and a larger percentage of patients requiring dosage reduction on the 6-week regimen. We conclude that the 3-week regimen is superior due to its improved tolerance and is recommended especially for combination drug therapy.