The effects of intermittent inhalation of 57 ppm nitric oxide (NO) were studied in eight anesthetized, ventilated pigs given a continuous infusion ofEscherichia coliendotoxin. Seven animals served as controls. By administering NO synchronized with inspiration and close to the orotracheal tube, measurable amounts of the toxic metabolite, NO2, in the inspiratory gas mixture were avoided. No direct systemic effects of NO inhalation were seen, but through counteracting pulmonary vasoconstriction, a fall in cardiac output was delayed. Nitric oxide effectively attenuated the initial peak rise in mean pulmonary artery pressure and resistance, both returning to control levels after cessation of NO. These effects were reproduced during later phases of endotoxemia, giving further proof to the role of gaseous NO as a selective pulmonary vasodilator. Nitric oxide diminished pulmonary shunting, but unimpaired oxygenation was preserved only during the first inhalation period. Leukocyte counts decreased drastically and platelet aggregation was enhanced, but after 1.5 hours of endotoxin infusion, platelet hyperaggregation was maintained in the NO group while it decreased in the control group.