The potent vasoactive and leukotactic properties of acetyl glyceryl ether phosphorylcholine (AGEPC) were further characterized histologically. After intravenous infusion of colloidal carbon and local injection of AGEPC, microscopic examination of rat cremaster muscle and skin revealed histamine-like vascular labeling restricted to postcapillary venules. Ultrastructural studies demonstrated subendothelial carbon accumulation in labeled venules. In rat skin, vascular labeling with colloidal carbon was an equally sensitive indicator of AGEPC-induced vasoactivity as was Evans blue dye extravasation for the assessment of AGEPC-induced increased vascular permeability (i.e., 1 pmole of AGEPC consistently initiated both vascular labeling and increased vascular permeability). In addition to its potent vasoactive effects in rabbits and rats, concomitant leukocyte emigration was observed in venules within 15 minutes after intradermal injection of AGEPC. In rabbit skin, AGEPC was equally as potent for the induction of leukocyte infiltrates as for the stimulation of increased vascular permeability. However, the vasoactive properties of AGEPC appeared to be neutrophil independent as well as independent of mast cell and platelet stimulation; these data suggest that AGEPC may act upon the microvasculature by direct stimulation of the venular endothelial cells. Thus, the putative role of AGEPC as a potent inflammatory mediator includes both the vasoactive and the leukotactic aspects of the acute inflammatory process.