The vasodilator effects of adenosine injected into the femoral artery (i.a.) of rabbits were analyzed. Single bolus i.a. doses of adenosine (0.3-10 microg) and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) (0.03-1 microg), an adenosine A2-receptor agonist, produced dose-dependent increases in femoral blood flow and decreases in resistance, almost without affecting blood pressure, heart rate, left ventricular (LV) pressure, and LVd P/dt max, even though CPCA elicited slight decreases in arterial blood pressure and LV pressure. On the other hand, bolus i.a. injections of N6-cyclopentyladenosine (CPA) (1-30 microg), an adenosine A1 receptor agonist, caused a relatively weak increase in blood flow, but markedly affected cardiac parameters, especially heart rate and LVd P/dt max. I.v. treatment with 3,7-dimethyl-1-propargylxanthine (DMPX)(2 mg kg(-1)), an antagonist of adenosine A2 receptors, or 8-phenyltheophylline (1 mg kg(-1)), an antagonist of adenosine A1 receptors, significantly attenuated the vasodilator response to adenosine, but not that to acetylcholine. Decreases in blood pressure, heart rate, LV pressure, LVdP/dt max and femoral vascular resistance, and increases in the blood flow elicited by CPA were not significantly modified by the DMPX treatment, but when this was combined with 8-phenyltheophylline, the responses to CPA were completely abolished. The present results indicate that the adenosine-induced femoral vasodilatation in rabbits may be mediated throughout activation of both adenosine A1 and A2 receptors.