P-selectin is an adhesion molecule for myeloid cells that seems to be essential for the development of cellular inflammatory responses. We show that adhesion of neutrophils to purified and recombinant P-selectin enhances the phagocytosis of unopsonized zymosan particles as judged by the number of cells ingesting particles (30.2 +/- 5.8 vs 14.5 +/- 4.0, p = 0.002) and the number of particles ingested per cell (percentage increase 58.3 +/- 4.4%. p = 0.0002). The enhanced phagocytosis was inhibited by Abs to CD18 or CD11b, suggesting that P-selectin alters beta 2-integrin function. The enhancement was only seen in the presence of cations allowing the integrin to assume a particular extracellular conformation. Furthermore, P-selectin, although not altering the total expression of CD18 on neutrophils, significantly increased the binding of mAb 24, which detects an activation-dependent epitope. Our results support a signaling role for P-selectin in influencing beta 2-integrin function.