Propylene glycol is commonly used as a vehicle for drug administration. In experiments involving the measurement of pulmonary hemodynamics, pentobarbital anesthesia routinely resulted in pulmonary hypertension in sheep. Since pentobarbital is formulated with 40% propylene glycol, we studied the pulmonary hemodynamic effects of propylene glycol in halothane-anesthetized sheep. Intravenous 40% propylene glycol (0.12 ml/kg over 3 min) rapidly increased pulmonary artery pressure (from 10 +/- 2 to 18 +/- 1 mm Hg; p less than 0.01) and pulmonary vascular resistance (from 200 +/- 18 to 500 +/- 51 dyn.s.cm-5; p less than 0.01); pulmonary hypertension was still present 1 h later. In sheep pretreated with the selective thromboxane A2 synthesis inhibitor dazmegrel, propylene glycol did not affect pulmonary artery pressure or pulmonary vascular resistance. Propylene-glycol-induced pulmonary hypertension in sheep appears to be mediated by thromboxane A2. Both ethanol and polyethylene glycol similarly produce pulmonary hypertension in sheep. We conclude that vehicle control data are required for studies using propylene glycol in sheep and advise caution when propylene glycol is employed as a vehicle in clinical use.