These studies were designed to test the hypothesis that adenosine and calcium are important in mediating radiocontrast-media-associated reduction in renal blood flow (RBF) in the dog. Intravenous verapamil (V) and diltiazem (DTZ) infusion significantly attenuated the magnitude of the vasoconstrictor response observed after each intrarenal contrast media (CM) injection. (First injection: -47 ± 8% control vs. - 14 ± 3% V, p < 0.03; -38 ± 4% control vs. - 19 ± 3% DTZ, p < 0.02. Second injection: -33 ± 6% control vs. -12 ± 1% V, p < 0.03; -32 ± 5% control vs. -17 ± 2% DTZ, p < 0.03. Third injection: -32 ± 6% control vs. -11 ± 5% V, p < 0.03; -38 ± 5% control vs. -10 ± 5% DTZ, p < 0.02.) Furthermore, V and DTZ almost completely abolished the increase in renal vascular resistance (RVR) induced by each CM administration. Theophylline also significantly attenuated the magnitude of the vasoconstrictor response observed after CM injection (first injection: - 31 ± 3% control vs. -12 ± 3% theophylline, p < 0.05; second injection: -26 ± 3% control vs. -12 ± 3% theophylline, p < 0.03). Similarly, theophylline blunted the increase in RVR induced by CM injection. In addition, theophylline inhibited exogenous adenosine-induced decrease in RBF (-61 ± 10% and -26 ± 1% decrease in RBF without and with theophylline, respectively). In contrast, dipyridamole significantly enhanced the vasoconstriction induced by CM (first injection: 25 ± 3% control vs. 49 ± 4% dipyridamole; second injection: 31 ± 3% control vs. 48 ± 4% dipyridamole p < 0.05). The effect of dipyridamole was abolished by simultaneous theophylline infusion. The vasoconstriction- induced CM was also enhanced during an ischemia (41 ± 11 vs. 28 ± 9%) induced by a reduction in renal perfusion pressure with an aortic clamp. Our data support the contention that endogenous adenosine and calcium action are essential for the effect of CM on RBF. We suggest that infusion of hypertonic radiocontrast agents result in an increase in sodium transport as has been documented with infusion of hypertonic saline with subsequent intrarenal generation of adenosine and activation of calcium-dependent vasoconstriction. Furthermore, our results in the ischemic kidney may explain why CM-induced acute renal failure occurs mainly in patients with preexisting renal failure. © 1990 S. Karger AG, Basel.