Migration of neutrophils through endothelial cells (EC) and induction of cytokine secretion are two well-documented events during the inflammatory reaction. The inflammatory, chemotactic cytokine interleukin-8 (IL-8) is secreted by EC in response to IL-1 stimulation. In this study, we show that platelets activated with either adenosine- 5'-diphosphate or epinephrine induce IL-8 secretion by EC. This stimulatory activity was found to be associated with sedimented platelets after activation. Blockade of IL-1 receptors on EC with IL-1 receptor antagonist (IL-1Ra) decreased the stimulatory effect of whole activated platelet preparations by 59% (P < .05). Similarly, IL-1Ra pretreatment of EC reduced the stimulatory effect of sedimented activated platelets by 60% (P < .01). In addition, we treated human blood donors with 750 mg of oral aspirin, and evaluated the stimulatory effect of epinephrine-activated platelets on IL-8 secretion by EC. IL-8 synthesis after aspirin ingestion was inhibited by 90% (P < .01) as compared with the preaspirin stimulation. These observations show that activated platelets induce IL-8 secretion via membrane-associated IL-1 activity, and provide a novel relationship between coagulation and inflammation that could be relevant to several diseases.