Fifty patients with advanced melanoma were perfused, using melphalan, dactinomycin, and mechlorethamine hydrochloride. At two years, one half of the patients are free from disease, and only one quarter have recurrence in the treated extremity. The first two years are critical for recurrences and metastasis, and the previous 21% five-year survival rate may be exceeded. Complications occurred in one third of the patients, but there were no deaths and no loss of limbs. Morbidity from complications did not persist more than six months. Previously, little improvement has occurred in the treatment of patients suffering from advanced melanoma, and revision of anticancer techniques and agents is necessary to insure the best patient treatment. This drug combination may have increased the effectiveness of regional chemotherapy such that some patients with advanced melanoma will obtain "clinical cures."