The aim of this study was to gain a thorough insight into the proliferative activity of benign and malignant melanocytic tumors. A total of 314 cases were examined by immunohistochemistry on paraffin-embedded material. The growth fraction was assessed by means of two monoclonal antibodies, Ki-S1 and Ki-S5, which react with two different proliferation-specific nuclear antigens. Additionally, HMB-45 was used as a marker of melanocytic activation. Statistically significant differences (P < 0.01) in the proliferation rates were found between common acquired nevi, Spitz's/Reed's nevi, primary cutaneous melanomas, and metastatic melanomas, whereas dysplastic nevi were hardly distinct from other nevi of the compound type. In melanoma, the growth fraction correlated well with the tumor stage but poorly with HMB-45 expression and mitotic count. Along with tumor progression, an increasing heterogeneity of proliferation indices was observed. Our results provide no evidence for a progression from dysplastic nevi into melanoma. They indicate that the assessment of the proliferative activity may be of considerable diagnostic help in cases of uncertain histology and that it might contribute to an alternative concept for the classification of melanocytic tumors.