Tumor necrosis factor (TNF alpha and TNF beta) and interleukin-1 (IL-1) are mediators of immunity and inflammation that induce different, but partially overlapping responses in human endothelial cells (HEC). We compared the effect of purified recombinant human TNF alpha, TNF beta and IL-1 on the production of platelet-activating factor (PAF) in HEC. After 30-60 min of treatment with TNF alpha or TNF beta, HEC produce and partially release considerable amounts of PAF, which reach a maximum after 4-6 h. In HEC treated with IL-1 PAF production is detectable after 2 h and peaks at 8-12 h. More than twice as much PAF is produced in response to optimal concentrations of TNF alpha than in response to TNF beta or IL-1. However, PAF synthesis is stimulated by lower molar concentrations of IL-1 than TNF alpha and TNF beta. The ability to induce PAF synthesis in HEC seems to be restricted to these three cytokines, as shown by negative results obtained with other cytokines that activate HEC (interferons, granulocyte- and granulocyte-macrophage colony-stimulating factor, epithelial growth factor, fibroblast growth factor, transforming growth factor beta), or participate in the inflammatory process (IL-6, platelet-derived growth factor).