Two subclasses of adenosine receptors, A1 and A2, have been described. The purpose of these experiments was to determine and compare the renal effects of several adenosine receptor agonists: adenosine (Ado), 2-chloroadenosine (2CA, nonselective), N6-cyclohexyladenosine (CHA, A1 selective), and N6-ethylcarboxamide adenosine (NECA, A2 selective). Rat kidneys were perfused at constant pressure (105 +/- 5 mmHg) using a Krebs-Henseleit buffer containing 3.5 g/100 ml Ficoll and 1.0 g/100 ml bovine serum albumin. Three clearance periods were obtained in each kidney, i.e., control, experimental [drug at 1 microM or vehicle (NaCl)], and recovery. Perfusate flow was increased by Ado, 2CA, and NECA but not affected by CHA. Glomerular filtration was increased by NECA, decreased by CHA, and not affected by Ado and 2CA. Afferent arteriolar resistance was decreased by NECA, increased by CHA, and unaffected by Ado and 2CA. Efferent arteriolar resistance was decreased by all agonists. CHA tended to decrease renin secretion whereas NECA significantly increased it. The results suggest that the renal vasculature possesses both A1 and A2 adenosine receptors and that activation of A2 receptors mediates arteriolar dilation and stimulation of renin secretion whereas activation of A1 receptors mediates arteriolar constriction and possibly inhibition of renin secretion.