A prospective randomized study was carried out to evaluate the effectiveness of additional regional cytostatic perfusion of the extremities in patients with malignant melanoma. In a control group (n = 54), the tumors were widely excised, and regional lymph nodes were dissected. The patients in the perfusion group (n = 53) received additional hyperthermic (42 degrees C) perfusion with Melphalan. The disease-free survival time was chosen as the criterion for evaluation. An intermediate analysis revealed a highly significant difference between the 2 groups (21 recurrences in the control group and 4 recurrences in the perfusion group, p less than 0.001). Therefore, the study was discontinued prematurely. In an analysis of the data performed after a median observation time of 5 years and 11 months, 26 recurrences were diagnosed in the control group, whereas 6 recurrences were noted in the perfusion group (p less than 0.001). The retrospective breakdown into different risk groups according to tumor thickness also demonstrates a significant difference. For patients with a primary tumor of 1.5-3.0-mm in thickness, 2 of 25 in the perfusion group and 10 of 25 in the control group have relapsed. For those with a primary tumor of greater than 3.0-mm in thickness, 4 of 28 in the perfusion group and 16 of 29 in the control group have relapsed. Eleven patients in the control group and 3 patients in the perfusion group have died due to metastatic spread of the melanoma (p less than 0.01). The results most clearly demonstrate the benefits of additional hyperthermic cytostatic perfusion.