Intravenous injection of Forssman antiserum produced a diphasic increase in pulmonary resistance in guinea pigs. The first increase (phase I) occurred with 20 sec latency after injection of Forssman antiserum. The second increase (phase II) occurred immediately thereafter, and this lasted more than 30 min and was irreversible. In the lung, hemorrhages and edema were evident. Hemorrhagic fluid was noted in the bronchiole and the alveoli. Polymorphonuclear leucocytes aggregated in the capillary lumen. The endothelial lining of the venule had been destroyed. Phases I and II were not blocked by DSCG. These were completely blocked by cobra venom factor and carrageenin. Isoproterenol, salbutamol and aminophylline selectively blocked phase I. Also, aminophylline weakly blocked phase II. Cyproheptadine blocked phase I, but chlorpheniramine did not. In contrast, indomethacin and aspirin selectively blocked phase II. Superoxide dismutase significantly blocked phase II, but inactivated superoxide dismutase and catalase did not. The present findings suggest that activation of the complement system appears to be essential for the induction of the increase in pulmonary resistance mediated by Forssman antiserum. Phase I is probably due to the contraction of the respiratory tract. Serotonin may be one of the substances for this contraction. In contrast, phase II is due to disintegration of the endothelial lining and extravasation of hemorrhagic exudates into the respiratory tract. Prostaglandins and/or superoxide radical may take part in the phase II response.