The opposing effects on blood pressure of clonidine and β-adrenoceptor antagonists which have been observed in some hypertensive patients were studied in conscious, spontaneously hypertensive rats. Daily treatment with clonidine (100 μ/kg, given by gavage) for 2 weeks significantly reduced systolic blood pressure and heart rate. After 2 weeks of treatment with clonidine, administration by gavage of d, l-propranolol (10 mg/kg daily) or sotalol (10 mg/kg daily) or intraperitoneal injection of H 35/25 [d, l-erythro-4-methyl-α-(1-isopropylaminoethyl)-benzylalcohol hydrochloride] (10 mg/kg daily) concomitantly with clonidine significantly counteracted the hypotensive action of clonidine. d-Propranolol, metoprolol, and atenolol (all 10 mg/kg daily) had no such effect. All drugs except d-propranolol and H 35/25, a selective β2-adrenoceptor antagonist, enhanced the bradycardic action of clonidine. These findings suggest that the pressor effect of β-adrenoceptor blocking agents during treatment with clonidine occurs at the level of β-adrenoceptors in the periphery.