Melanoma is an immunoresponsive malignancy. Interleukin-10 (IL-10) is a potent regulator of immunosuppression. The purpose of this research was to define the relationship of serum IL-10 to survival in patients with metastatic melanoma. Forty-one melanoma patients and 50 normal volunteers were analyzed. The median IL-10 level as determined by enzyme-linked immunosorbent assay (ELISA) in melanoma patients was 8.75 pg/ml compared to < 3.0 pg/ml in normal volunteers (p = 0.0001). Survival of melanoma patients with an IL-10 level above 10.0 pg/ml was 365 days compared to 557 days in patients with IL-10 levels less than 10.0 pg/ml (p = 0.0259, Wilcoxon). Elevated IL-10 levels were correlated with poor survival.