In metastatic melanoma S100 beta as well as melanoma inhibitory activity (MIA) are elevated in the serum in the majority of patients. Elevation has been found to correlate with shorter survival, and changes in these parameters in the serum during therapy were recently reported to predict therapeutic outcome in advanced disease. However, the value of these markers with respect to other possible markers by multivariate analysis has not yet been proven for individual patients. In this prospective study, S100 beta and MIA were measured in the serum of 67 consecutive patients before and following treatment. Analysing both the sensitivity and the specificity of the serum parameters by the areas under the receiver operating characteristics (ROC) curves, decreases in S100 beta and MIA during therapy were associated with response to therapy, while increases indicated progressive disease, Unexpectedly, the individual diagnostic value of changes in tumour markers during therapy was not superior to one-point measurements at restaging, Moreover, S100 beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis. Applying classification and regression trees (CARTs), one-point measurements of CRP was shown to be the most relevant overall parameter. (C) 2001 Lippincott Williams & Wilkins.