Reciprocal control of platelet function in the circulation has been proposed for the platelet-produced platelet proaggregatory prostanoid thromboxane A2 (TxA2) and the vascular endothelium-produced antiaggregatory prostanoid prostacyclin (PGI2). Forty drug-free healthy subjects were given a single dose of ibuprofen (0, 8, 10, 12, or 14 mg/kg) in a randomized, double-blind study. Blood samples were drawn 0, 2, 4, and 6 hours and 7 days after dosing for determination in serum (from untreated or in vitro indomethacin-treated portions of the blood) of TxA2 and PGI2 by radioimmunoassay of their stable metabolites (TxB2 and 6-keto-PGF1 alpha). Maximal platelet release of TxA2 (untreated serum) was lower in all drug groups 2, 4, and 6 hours after dosing. There was no significant decrease in PGI2 release. All doses of ibuprofen (except 0 mg/kg) induced essentially identical plasma levels at the times of measurement (postpeak decline), and effects could not be distinguished by dose for 8, 10, 12, or 14 mg/kg at these times. It is concluded that ibuprofen induces antiplatelet effects for at least 6 hours while preserving normal antiplatelet mechanisms.