We evaluated the effect of intrarenal arterial infusion of dibutyryl cyclic AMP on renal renin release. Dibutyryl cyclic AMP (300 micrograms/kg X min) produced significant and reversible increases in renin secretion rate, renal blood flow and urinary Na+ excretion. In the non-filtering kidneys, dibutyryl cyclic AMP increased renin secretion rate and renal blood flow. In indomethacin-treated dogs, dibutyryl cyclic AMP also produced significant and reversible increases in renin secretion rate and renal blood flow but had no effect on Na+ excretion. During infusion of dibutyryl cyclic AMP, infusion of the Ca ionophore A23187 failed to inhibit renin release. These findings suggest that the effect of dibutyryl cyclic AMP on renin release is not mediated by prostaglandins or intracellular Ca and does not involve the macula densa. We conclude that dibutyryl cyclic AMP has a direct effect on the juxtaglomerular cells.