Nine patients with metastatic malignant melanoma were entered onto a phase II trial consisting of WR-2721, 740 mg/m2 i.v. over 15 min, followed 15 min after completion by cisplatin, 100 mg/m2 i.v. over 30 min in 250 cc of 3% saline, on days 1 and 8 every 4 weeks. Six patients received two full courses of chemotherapy and were considered evaluable for response. No patients obtained a response. Toxicity, assessed according to the National Cancer Institute Common Toxicity Criteria, was acceptable and usually transient. However, fatigue, which manifested as a decrease in performance status, was significant in six of eight patients in whom this side effect could be evaluated. This subjective toxicity was most likely due to the high-dose cisplatin therapy. The lack of response in six fully evaluable patients allowed us to conclude with greater than 95% confidence that the combination of high-dose cisplatin and WR-2721 in a split-course day 1 and 8 schedule has a true response rate of less than 40%. In view of the relatively high subjective toxicity observed in our study and the more encouraging results observed by other groups using a different dose schedule of WR-2721 plus cisplatin, we do not recommend the use of high-dose cisplatin plus WR-2721 as employed in this trial.