Pentoxifylline (Pent) is a xanthine known to improve erythrocyte deformability and thought to have little effect on smooth muscle tone. In this study I examined the direct effects of Pent on the pulmonary vasculature of isolated lungs and compared them with the effects of aminophylline. The object was to study whether Pent can reverse the hypoxic pressor response (HPR) by its hemorheological property. Changes in pulmonary arterial pressure (Pa) of isolated lungs (pigs and rats) perfused at constant flow rate were monitored to reflect changes in vascular resistance. During normoxia, injection of Pent (5 mg/kg animal weight) in pig lungs depressed the Pa from 12.8 +/- 1.8 to 8.1 +/- 0.8 mmHg (1 mmHg = 133.3 Pa); whereas during hypoxia, Pa was depressed from 34.0 +/- 2.3 to 12.3 +/- 1.4 mmHg. To identify the mechanism of this vasodepressor effect (being either vasodilation or improved erythrocyte deformability), I tested the effect of Pent in lungs perfused with cell-free perfusate. In these plasma-perfused lungs, the vasodepressor effects of Pent were similar to those observed during blood perfusion (slight depression in Pa during normoxia, but large during hypoxia). Similar experiments in blood and plasma perfused pig lungs revealed that aminophylline (5 mg/kg) also produced similar vasodepressor responses. The effects of Pent in rat lungs were comparable; no effect during normoxia, but a depressor effect during hypoxia. Vasoconstriction in pig lungs induced by angiotensin infusion was also abolished by Pent.(ABSTRACT TRUNCATED AT 250 WORDS)