One hundred and fifty-six patients with extremity melanomas of known level or thickness who were perfused prophylactically with I-phenylalanine mustard (I-PAM) between January 1974 and December 1978 were studied retrospectively to determine the effect of variation of drug dosage and temperature on regional toxicity and disease control. The median drug dosage of 1-PAM for 57 patients undergoing axillary perfusion was 0.85 nig/kg (range 0.48-1.0 mg/kg) and the median dosage was 1.2 mg/kg (range 0.59-1.69 mg/kg) for 99 patients undergoing iliac perfusions. Sixty-five percent of patients achieved a maximum skin temperature of between 101" and 102ยฐF during perfusion. Determinate survival in the entire group was 93% at 5 years; 10% of patients developed positive regional nodes: and 2.5 % developed local or intransit metastases. Based on analysis of other series of patients with extremity melanoma with equivalent Clark's level 5-year determinate survival might be expected to be between 65 and 80%. The expected incidence of nodal metastases should be 19.1-24.0% and the incidence of local and intransit metastases should be 3-6%. While this series suggests a survival advantage for a series of extremity melanomas treated by regional chemotherapy when compared to other series treated by wide excision regional node dissection, the results obtained were independent of dosage of drug administered or maximal temperature attained over the range studied. This suggests consideration be given to exploring other dose ranges of drugs and heat in an effort to achieve equivalent control with lower regional toxicity.