Interleukin (IL)-10 is a pleiotropic cytokine with potent inhibitory effects towards T(H)-1 cells. IL-10 inhibits secretion of IL-2 and interferon (IFN)gamma by T cells and downregulates major histocompatibility complex antigens. A variety of tumor cells secrete IL-10, which can inhibit growth of tumor-specific cytotoxic T cells. IL-10 expression has also been detected in B-cell lymphomas and Hodgkin's disease (HD), and it has been suggested that the cytokine is involved in the pathogenesis of these tumors. We analyzed levels of IL-10 in pretreatment sera of 64 patients with HD and healthy controls using a sensitive enzyme-linked immunosorbent assay. Patients with biopsy-proven HD were enrolled in trials of the German Hodgkin Study Group (GHSG). Elevated IL-10 levels were detected in the sera of nine patients with HD (14.1%) (range 4.5-225.6 pg/ml with a mean of 61.5 pg/ml). IL-10 was not detectable in a control population of healthy volunteers (n =90). Multivariate analyses revealed a significant correlation between elevated IL-10 levels and higher age (over 45 years) but not with any other factors defined by the international prognostic factor score. Patients with elevated IL-10 levels had a significantly lower freedom from treatment failure rate as detected in univariate and multivariate tests. Thus, IL-10 may serve as an independent prognostic factor for HD patients.