Previous reports have shown that the intrarenal infusion of adenosine results in a relatively greater fall in superficial nephron glomerular filtration rate (GFR) than whole kidney GFR. This nonuniform decrease in GFR occurred despite a concomitant increase in total renal blood flow (RBF); thus, the present study was undertaken to assess the effect of intrarenally administered adenosine on the distribution of RBF. RBF distribution was measured with radiolabeled microspheres (15μn)in anesthetized dogs (n = 8) before and during the intrarenal artery infusion of adenosine (0.3 μmol/min). In dogs with elevated plasma renin activities (PRA), adenosine infusion produced no significant change in outer cortical blood flow (4.36 ± 0.50 vs. 4.41 ± 0.63 ml/min per g), whereas absolute inner cortical blood flow increased by 94% (1.54 ± 0.34 vs. 2.99 ± 0.52 ml/min per g). In dogs with low PRA, outer cortical blood flow was only minimally affected by adenosine infusion (6.39 ± 0.44 vs. 5.88 ± 0.33 ml/min per g), whereas inner cortical blood flow was increased from 4.91 ± 0.43 to 6.06 ± 0.38 ml/min per g. Although adenosine resulted in a deep cortical vasodilation in dogs with both high and low PRA (94% vs. 23%), the relative change was greater in the animals with high PRA. Additional experiments were performed in indomethacin- (or meclofenamate-) treated(n= 14) or phenoxybenz-amine-treated (n = 5) dogs to determine whether the deep cortical vasodilation is mediated by increased prostaglandin production or by inhibition of norepinephrine release. The increase in deep cortical flow during adenosine administration was not affected by either the blockade of prostaglandin synthesis or α-adrenergic receptors. We conclude that the effect of adenosine to preferentially dilate vessels of the inner cortex is independent of a prostaglandin-related or sympathetic adrenergic mechanism.