Abstract Although polymorphonuclear leukocytes (PMN) play important roles in the pathogenesis of inflammation, only limited information is available about their effect on hemodynamics. To elucidate the role of PMN in the regulation of systemic circulation, the effect of monoclonal anti-PMN antibody (RP3), which depletes the circulating PMN on the blood pressure, was studied in the rat. Intravenous administration of RP3 markedly decreased the blood pressure of the rat in a biphasic manner: a rapid phase followed by a slower phase. N ω -nitro- l-arginine, an inhibitor for nitric oxide synthase, inhibited the depressor effect of RP3, particularly at the slower phase; the inhibitory effect was not apparent at the rapid phase. Intravenous administration of RP3 did not decrease the blood pressure of the rat in which PMN had been depleted by intraperitoneal injection of RP3. However, transfusion of freshly isolated PMN induced hypotension in PMN-depleted rats. TCV309, an antagonist for platelet activating factor (PAF), inhibited the depressor effect of RP3. These results suggested that PMN might play important roles in the regulation of the circulatory status, particularly when their membrane surface was stimulated by various ligands, such as RP3.