Twenty-three patients with advanced colorectal carcinoma, previously treated with chemotherapy, were entered in a phase II trial of DON (6-Diazo-5-Oxo-L-Norleucine), an antagonist of L-glutamine. One of 14 adequately treated patients had a partial response of 6 weeks duration. The dose-limiting toxicity was nausea and vomiting; 48% of patients originally entered on the study withdrew because of vomiting. Myelosuppression was minimal, with only mild thrombocytopenia noted. The dose and schedule used in this study were beyond the maximally tolerated dose for many patients; future phase II studies of DON will be difficult to complete unless schedules and doses are found which result in less nausea and vomiting.