Recently, serum was shown to contain a factor that increased expression of the complement receptor CR3 on neutrophil membranes. This factor was localized to platelet granules and was released during coagulation. This study was undertaken to identify this factor in platelet granules. Platelet supernatants containing granule contents were incubated with neutrophils, and CR3 expression was determined by flow cytometry. Incubation with platelet supernatants induced more than a twofold increase in the amount of CR3 expressed on the neutrophil membrane (p = 0.05). Anti-platelet-derived growth factor (anti-PDGF) Fab, when preincubated with the platelet supernatants, completely inhibited this CR3-inducing activity. Pure PDGF induced a dose-response increase in CR3, whereas platelet factor 4 had no effect. PDGF was active in concentrations well within the physiologic range. These data indicate that PDGF is responsible for the CR3-inducing activity of platelet supernatants. PDGF may well be an important regulator of neutrophil adherence and phagocytic function in areas of tissue injury.