We examined the effects of platelet-activating factor (PAF) on lung epithelial permeability by measuring the clearance of intratracheally administered 99m-technetium-labeled diethylene triamine penta-acetic acid (99mTc-DTPA) in guinea-pigs which were anaesthetised, paralysed and mechanically ventilated. The clearance of the radiolabeled tracer molecule 99mTc-DTPA from airways to the blood was expressed as changes in counts/min corrected for background. For each guinea-pig, 99mTc-DTPA clearance was assessed before and after i.v. PAF administration, when tracheal pressure had returned to near control values. Doses of 10, 50 and 100 ng/kg of PAF caused dose-dependent increases in 99mTc-DTPA clearance of 7 +/- 3%, 38 +/- 7% and 65 +/- 11% respectively. The respective effects of 0.5 mg/kg of the beta 2-adrenergic agonist salbutamol and 0.3 mg/kg of the alpha 1-adrenergic agonist methoxamine on the increase in lung epithelial permeability induced by 50 ng/kg PAF were also studied. Salbutamol significantly reduced the acute bronchoconstrictor effects of PAF, but did not affect the increase in lung epithelial permeability, which was 58 +/- 10%. Conversely, methoxamine significantly enhanced the bronchoconstrictor effects of PAF but inhibited the lung epithelial permeability increase, which was only 10 +/- 13%. In the absence of PAF, salbutamol significantly increased this permeability by 49 +/- 11%, whereas methoxamine alone slightly reduced, it by -11 +/- 4%. These results demonstrate that PAF increases lung epithelial permeability and suggest that vascular surface area recruitment may explain this increase.