We have previously reported that captopril stimulates thromboxane A2synthesis in patients with essential hypertension. In the present study, the hypotensive effects of captopril and OKY-046, a selective inhibitor of thromboxane A2synthetase, were studied in nine patients with essential hypertension to determine whether thromboxane A3 is involved in the regulation of blood pressure. A single oral dose of OKY-046 (400 mg) decreased urinary thromboxane B2(a stable metabolite of thromboxane A]) excretion significantly (from 113 ± 19.0 to 51.0 ± 6.1 pg/min;p< 0.01) and increased urinary sodium excretion significantly (from 73.0 ± 15.3 to 113.0 ± 14.4 μ.Eq/min;p< 0.01), but no change was observed in mean arterial pressure. The administration of OKY-046 (600 mg/day) for 3 days induced a significant and sustained decrease in urinary thromboxane B2excretion, but it did not affect the mean arterial pressure. Although captopril (50 mg) alone induced a significant increase in urinary thromboxane B2excretion (from 91.4 ± 11.0 to 297.3 ± 30.8 pg/min;p< 0.001) and a significant decrease in mean arterial pressure (from 97.0 ± 4.7 to 88.1 ± 5.1 mm Hg;p< 0.01), captopril in combination with OKY-046 induced a decrease both in urinary thromboxane B2excretion (from 70.8 ± 12.3 to 54.2 ± 14.7 pg/min;p< 0.01) and in mean arterial pressure (from 105.1 ± 3.8 to 84.2 ± 3.6 mm Hg;p< 0.01). Thus, the hypotensive effect of captopril was potentiated by OKY-046. OKY-046 did not affect the changes in plasma renin activity and plasma aldosterone concentration and blunted urinary prostaglandin E2and 6-keto-prostaglandin F, a excretion in response to captopril. These results indicate that thromboxane A2counteracts the hypotensive effect of captopril in patients with essential hypertension.