Regional cerebral blood flows and shunting of microspheres with four different sizes (9,12, 16 and 25 microns) into the superior sagittal sinus were determined in twelve dogs. Venous blood was collected from the superior sagittal sinus for 120 min after the injection of microspheres, and the dogs were then sacrificed immediately. Results on blood flow measurements and venous shunting determinations were similar between left ventricular and left atrial injections. Blood flows measured by 12, 16 and 25 microns spheres were comparable in various brain tissues, except the choroid plexus. 9 microns spheres underestimated blood flows in all regions studied: by 13–19 percent in the cerebral cortex, midbrain, brain stem and cerebellum, by 34–42 percent in the cortical white matter, corpus callosum and cervical cord, and by 64–81 percent in pituitary gland and choroid plexus. These results probably reflect regional difference in microvascular architecture. Venous shunting of 9, 12, 16 and 25 microns spheres during a 24 hr period were 23.6 +/− 2.5, 12.6 +/− 1.2, 4.8 +/− 1.4, and 4.0 +/− 1.2 percent (mean +/− SEM), respectively, with respect to the arterial delivery. Although most of the venous shunting occurred during the first 3 min after the injection of microspheres, it continued 3–60 min after the injection. Beyond 60 min, the venous shunting became minimal for 16 and 25 microns spheres, while significant amount of 9 microns spheres continued to appear in sagittal sinus. This time dependent shunting indicates that some microspheres may be transiently trapped in the microcirculation and become gradually dislodged with time. Failure to consider this time dependence may underestimate the shunting of microspheres through the microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)