The National Cancer Institute of Canada Clinical Trials Group carried out a phase II trial of trimetrexate given in a daily x 5 intravenous bolus schedule every 3 weeks in patients with measurable metastatic malignant melanoma who had not received previous chemotherapy. Significant hematologic toxicity was observed and was not obviously related to the dose of trimetrexate. No responses were seen in 18 patients. We did not find trimetrexate given as described to be effective in metastatic malignant melanoma.