ABSTRACT.Marked leukopenia and sequestration of granulocytes in the lung are consistently seen in serve early onset group B streptococcal (GBS) disease in human infants. To investigate the role of granulocytes as potential mediators in the pulmonary pathophysiology of this disease, the effects of intracenously adminstered GBS type III toxin were studied in young lambs before and after granulocyte depletion with hydroxyurea. Granulocyte depletion markedly reduced the 4-fold increase in total lung resistance and the decrease in dynamic compliance observed after GBS toxin. Granulocyte depletion significantluy attenuated the pulmonary hypertension, hypoxema and increased minute ventilation present during the first phase of the response (0.5-1 h after GBS toxin). It did not significantly alter the increase in lung lymph flow and protein clearance during the second phase of the response (3.5-5 h after GBS toxin). The result indicates that granulocytes are involved as, mediators of the changes in lung mechanics seen after GBS toxin infusion in young lambs. Granulocytes contribute to the pulmonary hypertension and decrease in arterial oxygenation, but other mediators appear to be responsible for the injury of the vascular endothelium.