In the present study serum levels of S-100 protein beta were measured in 643 patients with cutaneous malignant melanoma. An immuno-radiometric assay with three monoclonal antibodies against bovine S-100 protein beta subunit was used. At the time of blood sampling 553 patients were in clinical stage 1, 24 in clinical stage II and 66 in clinical stage III. The overall survival rate was strongly associated with serum levels of S-100 protein. The observed/expected death ratio was markedly increased with increasing levels of S-100 beta (p < < 0.001). Our data strongly suggest that S-100 beta in serum is an independent prognostic marker and may be useful in identifying high-risk cases and monitoring response to therapy in patients with malignant melanoma.