Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied. Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 microg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 micromol x L(-1)), collagen (2.5 and 5 microg x mL(-1)), epinephrine (1.25 and 5 micromol x L(-1)) and arachidonic acid (0.5 mg x mL(-1)) was measured. Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 micromol x L(-1), epinephrine (1.25 and 5 micromol x L(-1)) and collagen (2.5 microg x mL(-1)). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3+/-1.2 to 31.8+/-1.2 nmol x L(-1), remained increased at 4 h (29.2+/-1.3 nmol x L(-1)) and normalized at 6 h (27.4+/-1.1 nmol x L(-1)). Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.