The interaction between human endothelial cells and leukocytes during immunologic and inflammatory responses is in part mediated through the release of soluble mediators. We report that cultured human umbilical vein endothelial cells secrete IL-6 when stimulated with LPS. This effect was inhibited by polymyxin-B. The monokines IL-1 and TNF-alpha were also potent inducers of IL-6, whereas lymphotoxin was only effective at much higher concentrations. Endothelial cell supernatant IL-6 was active as hybridoma-plasmacytoma growth factor and as B-cell stimulating factor. Endothelial IL-6 activity was neutralized by a specific anti-IL-6 antibody and by immunoprecipitation it was shown to be identical in size to human fibroblast-derived IL-6. As IL-6 is possibly an important regulator of host defense responses, production of this cytokine by endothelial cells may contribute to the pathogenesis of various inflammatory and immunologic diseases.