In patients with advanced or recurrent melanoma confined to a limb, hyperthermic isolated limb perfusion (ILP) with melphalan produces complete remission in 35-40% of cases and partial remission in a further 35-40%. Mild or moderate limb toxicity is usual, but severe toxic reactions in the limb sometimes occur. After preliminary reports suggested that cisplatin administered by ILP was even more effective than melphalan yet less toxic, a study was undertaken to further assess the value of hyperthermic ILP with cisplatin in the management of limb melanoma. Ten patients were treated. The procedure failed to eliminate melanoma in the limb in 5 of the 6 who received therapeutic ILPs for recurrent disease, and recurrence developed in 2 of the 4 patients who received prophylactic ILPs. Toxicity in the perfused limbs was unacceptably high, with 2 of the 10 patients having severe reactions, one necessitating amputation. We conclude from the results of this study and from a review of literature that neither cisplatin nor any other drug or drug combination so far used for ILP in melanoma patients achieves results which are clearly superior to those achieved with melphalan. Studies are currently in progress investigating double perfusion protocols, new strategies with regional hyperthermia, and the administration by ILP of biological response modifiers such as tumor necrosis factor and interferon. However, for the present, hyperthermic ILP with melphalan remains the treatment most likely to be successful in eliminating or controlling advanced or recurrent melanoma in a limb.