To assess the clinical and prognostic relevance of serum S-100 beta in malignant melanoma serum levels of S-100 beta protein were measured in 84 patients with malignant melanoma. Using a cut-off value of 0.3 microgram/L the sensitivity was 0% (none of 36) in patients with stage II, 31% (four of 13) in patients with stage III and 69% (24 of 35) in patients with stage IV. In the reference group serum S-100 beta was below 0.3 microgram/L in all cases (specificity = 100%). A significant correlation existed between serum S-100 beta values and clinical staging as well as survival. In patients with distant metastases the serum concentration of S-100 beta protein correlated well with the number of affected organs. Serial measurement in these patients revealed that tumour progression was accompanied by rising S-100 beta values whereas declining values could only be revealed in one patient with a dramatic clinical response to therapy. Our results suggest that serum S-100 beta determination is a useful marker for the evaluation of prognosis in patients with metastatic malignant melanoma and should be included in the clinical staging.