Endralazine (BQ 22-708, Miretilan) and guanfacine (BS 100-141, Estulic) were tested alone and in combination for their effects on blood pressure and heart rate in conscious spontaneously hypertensive rats and conscious normotensive dogs. During combined administration of endralazine and guanfacine to spontaneously hypertensive rats, guanfacine 1 mg kg-1 i.v. blocked the tachycardia caused by endralazine, 1 mg kg-1 i.v. After oral administration, the tachycardia induced by 0.5 and 1 mg kg-1 of endralazine was inhibited dose-dependently by 0.05, 0.1 and 0.5 mg kg-1 of guanfacine. The antihypertensive efficacy of endralazine was either unchanged or increased by guanfacine at 0.05-1 mg kg-1. In normotensive conscious dogs, 0.2 mg kg-1 i.v. of guanfacine antagonised the tachycardia elicited by 0.3 mg kg-1 i.v. of endralazine. The elimination of the endralazine-induced reflex tachycardia by guanfacine suggests that the combination of both drugs could be useful in antihypertensive therapy.