Background: Metastatic melanoma shows different local response rates in organs to systemic or local treatment modalities. Whereas skin, soft tissue, lymph node and lung metastases seem to have better local response rates, the local response of metastases localized in the liver, brain and bone seems to be low. Objectives: The organ- specific response rate, local response rate of each therapeutic measure and survival of 68 patients with stage IV disease were evaluated. Methods: Four hundred and ten treatment periods (1- 18 per patient) in 17 different organs of 43 men and 25 women (mean age 55 years, range 19- 79) with measurable, widespread, surgically incurable disease were analysed. Chemotherapy was given in 405 of 410 treatment periods with dacarbazine, fotemustine, vindesine, carboplatin and temozolomide in different schedules. Local treatment modalities comprising radiotherapy, gamma knife radiosurgery and local hyperthermia were given in 71 of 410 treatment periods. Results: Local response (complete or partial local remission) was achieved in 52 treatment periods (12.7% ). When local treatment modalities, either combined with systemic therapy or not, were compared with systemic therapeutic modalities alone, a local response of 24% was achieved with local measures, compared with 10% in systemic treatment only (P=0.003). When a spontaneous remission rate of less than 5% is considered, however, local as well as systemic treatments had a significant effect (P<0.001). Organ- specific response rates to local therapies showed no statistically significant differences between the various organs involved. When systemic treatments without local measures were taken into account, lung metastases, cutaneous/subcutaneous metastases and adrenal metastases performed significantly better than liver metastases. When different treatment modalities were considered, there was no significant difference between the three local measures applied (radiotherapy, gamma knife radiosurgery and hyperthermia). Among the systemic therapies, dacarbazine high dose and carboplatin monochemotherapywere superior to combined regimens using fotemustine. A local response, irrespective of the mode of therapy, was significantly associated with longer survival (median 16 months) compared with no local response or local progressive disease (median 7 months; P<0.0001). When the first treatment period of each patient was considered, local responsewas no longer a significant predictor. Conclusions: The study shows that local therapeutic measures are superior in inducing a local response than systemic therapies alone. Induction of remission may be associated with longer survival. Chemotherapy, despite limited local response rates, is still statistically superior to an estimated spontaneous remission rate.