From 1978 to 1990, 32 patients with Clark V melanoma were treated by wide excision of the primary and adjuvant regional isolated perfusion with melphalan. M.D. Anderson stage of disease was stage I in 22 and stage IIIb in 10 patients. Five-year survival rates were 58% and 27%, respectively. Seven patients developed a recurrence in the perfused limb [stage I, 2, stage IIIb, 5 patients (P = 0.03)], and 4 of 17 patients developed regional lymph node metastases. Of the well-known prognostic variables, only ulceration of the primary tumor significantly influenced survival (P = 0.03). We did not see any improvement in survival rates compared with literature data on nonperfused patients. In the absence of data on locoregional recurrence rates in nonperfused Clark V melanoma patients, we cannot say whether adjuvant perfusion diminished this risk. Therefore, the results of the prospective randomized EORTC/WHO trial in primary high-risk extremity melanoma have to be awaited.