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The 3H-thymidine labeling index (LI) was determined on 178 lesions, four of which were primary, from 129 patients with malignant melanoma. The overall analysis showed a wide variability of LI values, from 0.01% to 31.7%, with an exponential distribution and a median value of 8.0%. Similar median LI values were observed for the various metastatic sites, and no difference was found between patients who only had surgery and those who also received systemic therapy. Cell kinetics and patient age and sex were not related in terms of extent and type of nodal involvement. Conversely, a trend toward higher proliferative activity was observed in amelanotic (8.3%) than in melanotic (5.9%) lesions (P = 0.08). The follow-up study on a series of 48 Stage II patients has shown a higher probability of 2-year survival for patients with slowly proliferating tumors than for those with rapidly proliferating tumors (86.9% versus 40.4%, P = 0.054). Along with this finding, the absence of a relationship between cell kinetics and both the main host and tumor characteristics indicated that cell kinetics was a prognostic variable and could be an important tool in the evaluation of patients with metastatic melanoma.