Pulmonary leukostasis, as a result of complement activation, has been invoked as a cause of pulmonary dysfunction. To investigate this phenomenon, we studied the pulmonary response to infusion of autologous complement-activated plasma in sheep and rabbits. Complement activation was produced by plasma incubation with zymosan. Leukopenia, with selective loss of polymorphonuclear leukocytes into the lungs, occurred in all animals immediately after the onset of plasma infusion. Complement-activated plasma infusion in sheep produced a significant fall in the arterial Po2and a marked rise in pulmonary vascular resistance, whereas no such effects were observed in rabbits. Pretreatment of the sheep with sulfinpyrazone eliminated the pulmonary response to complement-activated plasma without altering the leukopenic response. Pulmonary histology in rabbits and sheep confirmed the presence of intracapillary leukostasis after the plasma infusions, whether or not sulfin-pyrazone had been administered previously. The pulmonary response to complement activation is associated with pulmonary capillary leukostasis, but leukostasis alone is not an adequate explanation of the phenomenon. Circ Res 46:175-180, 1980