We studied the effects of prostacyclin (PGI 2) on the airway responses to platelet-activating factor (PAF) in a randomized and crossover study in eight normal subjects. PGI 2 or diluent (glycine buffer) was continuously infused on 2 separate days. Two breaths of PAF (21 μg) were inhaled three times every 15 minutes and airflow at 30% of vital capacity from partial flow-volume curves (Vp 30) was measured. PGI 2 (4 ng/kg/min) had no effect on Vp 30 or blood pressure, whereas heart rate increased from 70.3 ± 3.9 to 73.7 ± 4.0 beats/min (mean ± SEM; p < 0.01). Two subjects did not complete the study because of transient hypotension. PGI 2 had no effect on PAF-induced bronchoconstriction with maximal decreases in Vp 30 of 42.0 ± 8.0% ( p < 0.01) during PGI 2 and 49.8 ± 14.2% ( p < 0.02) during diluent infusion. Ex vivo platelet aggregation to PAF (10 −9 to 10 −7 mol/L) was significantly inhibited by PGI 2. Circulating neutrophils decreased from 4.7 ± 0.9 × 10 9 /L to 1.5 ± 0.3 × 10 9/L ( p < 0.05) 5 minutes after the first PAF inhalation during diluent infusion, whereas there was no significant change with PGI 2. Thus, PGI 2 does not influence PAF-induced bronchoconstriction in man despite causing marked inhibition of ex vivo PAF-induced platelet aggregation and preventing the fall of neutrophils.