The aim of this study was, first, to examine pressure effects of platelet-activating factor (PAF) on pulmonary vasculature and bronchi in isolated perfused and ventilated rat lungs and, second, to investigate pulmonary uptake of tritium-labeled PAF injected into the pulmonary artery. Four different perfusates were used: Krebs-Ringer solution (KRS) and KRS with 0.2, 2.0, and 4% albumin. In the KRS, perfusion and inflation pressure increased by 100 and 47%, respectively, after 100 micrograms PAF. By increasing the albumin concentration, the pressure effects were reduced significantly (P less than 0.01). These changes were paralleled by increasing tritium outflow rates (15.9 +/- 3.6, 49.7 +/- 12.5, 78.3 +/- 8.7, 87.8 +/- 2.6%, respectively). Comparable changes in tritium outflow rates (19.2 +/- 3.9, 38.2 +/- 7.2%) occurred when tracer amounts of labeled PAF were injected, but, in KRS with 2.0 and 4.0% albumin, tritium outflow was significantly lower (52.8 +/- 8.0 and 60.8 +/- 11.8%, respectively). Pressure effects are related to extraction rates. Both pressure effects and extraction rates depend on binding to the albumin in the perfusion medium used. PAF might act on smooth muscle tissue of the pulmonary vasculature. Inflation pressure increases are probably due to concomitant occurrence of edema.