OBJECTIVE Our objective was to develop a method to correct for the effect of partial volume averaging (PVA) in the CT measurement of contrast enhancement in small arteries, and to validate a dynamic contrast-enhanced CT method for the measurement of regional cerebral blood flow (rCBF). METHODS Contrast-enhanced CT scans of tubes of known inner diameters were obtained to estimate the size-dependent scaling factors (PVSF) due to PVA. The background-subtracted image profiles of the contrast-filled tubes were fitted to gaussian curves, and the standard deviations (SDs) of these curves were correlated with the PVSF of each tube. In the second part of this investigation, 13 studies were performed in six New Zealand white rabbits under normal conditions. Dynamic CT measurements of rCBF, regional cerebral blood volume (rCBV), and regional mean transit time (rMTT) were calculated in the left and right parietal lobes and the basal ganglia. The CT rCBF values were compared with those obtained by the microsphere method, which is the standard of reference. RESULTS We found strong correlations for the SDs of the gaussian curves to the known inner diameters of the tubes and to their size-related PVSF. These correlations demonstrated that the error from PVA in the measurement of arterial enhancement can be corrected without knowledge of the actual size of the artery. The animal studies revealed a mean (+/- SD) rCBF of 73.3 +/- 31.5 mL/100 g per minute, a mean rCBV of 1.93 +/- 0.74 mL/100 g, and a mean rMTT of 1.81 +/- 1.02 seconds. A strong correlation was found between rCBF values derived by the CT and the microsphere methods. CONCLUSIONS We have validated a new dynamic CT method for measuring rCBF. The accuracy of this technique suggests that it can be used as an alternative diagnostic tool to assess the cerebral hemodynamics in experimental and clinical situations.