Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart On each occasion, they received two doses of either placebo or ridogrel (300 rag) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A 2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B 2 , 6-oxoprostaglandin F lo , and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A 2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B 2 and thromboxane Bj compared with placebo (21 ±6 versus 279±28 and 14±4 versus 39±9 ng/g creatinine, respectively, P<.0001 and P<.05). Excretion of 2,3-dinor-6-oxoprostaglandin F 1(r and 6-oxoprostaglandin F, o was increased by ridogrel compared with placebo (184±20 versus 146±11 and 86±9 versus 58±6 ng/g creatinine, respectively; P<.0S). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P<.0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A 2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure. (Hypertension 1993^22:197-203)