The optimal single dosage of melphalan in isolation perfusion of the limbs for malignant melanoma was assessed. For this purpose a method to determine the volume of the isolated region in the individual patient and a grading system for the reaction of the normal tissues were introduced. A strictly standardized pharmacosurgical routine was developed that permitted an analysis of the correlation between dosage and the grade of toxic reaction in 90 perfusions. The optimal dosage of a cytostatic drug was considered to be the highest amount tolerated at an acceptable risk. Melphalan at 10 mg/l perfused tissue was determined as the likely optimum. This dose provoked remarkably little variation in toxicity, all reactions falling within a safe range. No exception to the applicability of this dosage was encountered.