6-Thioguanine was administered i.v. or orally to 66 patients on an intermittent schedule, 1 dose every 3 wk. Doses were gradually escalated until moderate toxicity was observed. The dose-limiting toxic effects were myelosuppression and azotemia. The recommended starting doses for phase II or III studies were 700 mg/m2 i.v. and 1400 mg/m2 orally. Nephrotoxicity and myelosuppression were reversible in all clearly drug-related instances. Myelosuppression was transient, with nadir blood cell counts observed 10-14 days after drug administration. No cumulative toxicity was observed. Antitumor responses were observed in 5 of 21 evaluable patients with metastatic colorectal carcinoma including 2 of 4 previously untreated patients with that disease. Other than a transient response in 1 patient with endometrial carcinoma who received her drug orally, all other responses were observed in patients treated i.v. with 6-thioguanine. Further phase II trials, particularly in colorectal carcinoma, are recommended.