5-S-Cysteinyldopa (5SCD), the precursor of pheomelanine, has been reported to be a reliable marker for occult melanoma metastases. The goal of this study was to investigate whether serum 5SCD is also a marker to follow the efficacy of treatment of melanoma patients.Serum samples were collected before and after each cycle of immuno- or immuno-chemotherapy from 1991 until 1995 from 11 patients suffering from metastatic melanoma. 5SCD was analysed by HPLC and electrochemical detection.All patients showed 5SCD levels above the upper limit of the normal range. The mean level of all patients was 2.3 times at the start of therapy and at the end of therapy 50.7 times higher than that of a healthy collective. Increasing levels of 5SCD paralleling progression of metastastes were also observed in patients with amelanotic melanomas. Therapy cycles were characterized by decreasing or increasing 5SCD levels. From 41 cycles analysed 28 (68.3%) showed a decrease and 13 (31.7%) an increase. Using the logrank test and survivals curves according to Kaplan-Meier, patients with more than 68.3% decreasing cycles exhibited a statistically significant higher survival (p<0.008) than those with less than 68.3% decreasing cycles.5SCD is not only a marker for occurance and progression of metastases but also helps to control the response to therapy.