The effects of halothane versus isoflurane on distribution of cerebral blood flow (CBF) were compared using 14C-iodoantipyrine autoradiography. Sprague-Dawley rats were exposed to 1 MAC of either halothane (n = 8) or isoflurane (n = 7) in 33% O2/balance nitrogen for 55 min prior to determination of CBF. Normoxia, normothermia, and normocapnia were maintained throughout the experiment and mean arterial pressures (MAP) were held within the range of 90-100 mmHg by infusion of blood. Coronal autoradiographic brain images were then digitized and optical density values converted to CBF with the use of 14C autoradiographic standards and arterial radioactivity data. Hemispheric, neocortical, subcortical, and selected local anatomical regions were defined on a cathode ray screen display by cursor outline. Mean CBF for each region was determined at each of eight standardized coronal brain sections, and area weighted average values for the whole brain were also calculated. Hemispheric CBF was identical in the two anesthetic groups: halothane = 150 ± 16 ml·100 gm-1·min-1; isoflurane = 147 ± 19 ml·100 gm-1·min-1. However, neocortical CBF was greater in halothane anesthetized animals (halothane = 185 ± 16 ml·100 gm-1·min-1; isoflurane = 154 ± 19 ml·100 gm-1·min-1, P = .004). The authors conclude that halothane and isoflurane exert regionally selective effects on CBF with halothane appearing to have a more pronounced effect on the neocortex. Previously reported discrepancies concerning the relative effects of these two agents on CBF may be due to inherent differences in the tissue regions measured by the different techniques.