Mean arterial pressure and heart rate were measured during intra-aortic arch (i.a.a.), intravenous, and suprarenal artery (s.r.a.) infusions of adenosine in conscious, unrestrained normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in the absence and presence of ganglionic blockade. In both groups, i.a.a. and i.v. infusions of adenosine induced comparatively larger dose-dependent reductions in mean arterial pressure than did s.r.a. infusions. In WKY, i.a.a. and i.v. infusions of adenosine were equipotent in reducing mean arterial pressure. In contrast, i.a.a. infusion of adenosine was approximately twice as potent as i.v. infusion in SHR. Also, SHR were approximately 6.5 and 2.6 times more sensitive to i.a.a. and i.v. infusions of adenosine, respectively, than were WKY. Further, i.a.a. and s.r.a. infusions of adenosine caused tachycardia in WKY, while i.v. infusions did not alter heart rate. In SHR, neither i.a.a. nor s.r.a. infusion of adenosine altered heart rate, but i.v. infusion induced a profound bradycardia. In ganglionic-blocked WKY that received a norepinephrine infusion to restore blood pressure and heart rate to pre-ganglionic blockade levels, depressor responses to i.a.a. infusion of adenosine were unchanged while the increase in heart rate was abolished. In SHR, ganglionic blockade markedly decreased the depressor response to i.a.a. and i.v. infusions of adenosine and abolished the bradycardic response to i.v. infusion. These results suggest that adenosine is an effective hypotensive agent in both WKY and SHR; however, marked between-strain differences exist in the cardiovascular response to adenosine. These differences most likely are due to changes in adenosine-pulmonary interactions and increases in the importance of adenosine-autonomic interactions in SHR.