Granulocyte chemotactic protein/Interleukin-8 (GCP/IL-8), purified to homogeneity from endotoxin- or mitogen-stimulated human mononuclear cells, was injected intradermally into rabbits to evaluate the proinflammatory properties of this novel cytokine. In the presence of a vasodilator substance, pmol amounts of GCP/IL-8 induced neutrophil accumulation that was fast in onset, relatively short of duration (half life 60 to 70 minutes), and was associated with a parallel time course of plasma protein extravasation. GCP/IL-8-induced edema formation was found to be neutrophil dependent. These data provide evidence that GCP/IL-8 fulfills two important criteria for consideration as an inflammatory mediator. It is possible that endogenous GCP/IL-8, if produced locally by tissue macrophages, may contribute to the initiation of the inflammatory response to infection.