33 patients with advanced adenocarcinoma of the colon or rectum were treated with isophosphamide given intravenously at a dose of 4 g/m2 every 3 weeks. Patients receiving the full dose in a single infusion experienced severe nausea and vomiting and hemorrhagic icystitis. Those receiving two infusions of 2 g/m2 each 24 h apart, had only mild gastrontestinal and urinary symptoms. Hematologic toxicity was similar for both regimens, consisting of mild and transient leukopenia in approximately 30% of patients. Alopecia occurred in 60% of patients. Central nervous system toxicity manifested as somnolence and disorientation occurred in three patients. Only one objective tumor response lasting 9 weeks was noted in 33 patients treated with isophosphamide.