In this study we have examined the effects of interleukin-10 (IL-10) on blood mononuclear cells (MNC) and on skin as well as on synovial fibroblasts. In unstimulated MNC, we found that IL-10 is a potent stimulator of interleukin-1 receptor antagonist (IL-1ra) and monocyte chemoattractant protein-1 (MCP-1) production and an inhibitor of IL-8 release. In cells exposed to IL-1 beta, it also moderately stimulated IL-1ra production and release of soluble tumor necrosis factor receptor p75 (sTNF-R p75) and inhibited IL-8 and MCP-1 production. In addition, we have evidence that the biological effects of IL-10 are not restricted to hematopoietic cells. IL-10 stimulated sTNF-R p55 dose-dependently and inhibited MCP-1 release from IL-1 beta-activated fibroblasts, whereas IL-8 production was not affected. Taken together, these findings identify novel biological actions of IL-10 on blood mononuclear and connective tissue cells which support its regulatory functions as a suppressor of inflammatory processes.