Fast computed tomography (CT) is one of the few methods available to measure cortical and medullary renal blood flow (RBF) directly. Because these measurements are complicated by passage of the contrast medium into extravascular compartments, we used the residual opacity following the vascular blush as an index to account for extravascular iohexol. Kidneys of anesthetized dogs were examined in situ by fast CT following intra-aortic injections of iohexol. Perfusion was analyzed during a control period and three subsequent periods in which RBF was reduced by 10%, 30%, and 50%. Cortical microvascular distribution volume changed from 19.7 +/- 2.8% to 19.8 +/- 1.7%, 15.3 +/- 1.2%, and 9.9 +/- 1.7%, respectively, without significant alterations in cortical mean transit time. Microvascular distribution volume was divided by mean transit time to determine tissue perfusion. Cortical perfusion changed from 3.8 +/- 0.7 to 3.9 +/- 0.6, 3.1 +/- 0.5, and 2.2 +/- 0.5 mL.min-1.mL tissue-1. Total cortical blood flow (cortical perfusion multiplied by cortical volume) decreased from 164 +/- 32 to 159 +/- 31, 117 +/- 20, and 86 +/- 22 mL/min, respectively. Medullary microvascular distribution volume, mean transit time, perfusion, and total blood flow remained unchanged. Fast CT-determined total RBFs (cortex plus medulla) were similar to simultaneous electromagnetic flow measurements. These results indicate that renal regional perfusion is more dependent on the microvascular distribution volume than mean transit time and that variations in renal tissue perfusion with reduction of RBF are more apparent in the cortex than in the medulla.