This study evaluated the hypothesis that the peripheral sympathetic nervous system is one of the factors increasing the heterogeneity of venous O2 saturation in selective brain regions. Regional cerebral blood flow and O2 saturation were determined in the anterior cortex, posterior cortex, and medulla of either sham-operated or bilaterally sympathectomized Long-Evans rats. Cerebral venous O2 saturations, indicating the balance between local O2 supply and consumption, were found to be significantly more heterogeneous in the sham-operated group. In the anterior cortex, the coefficient of variation [100(SD/mean)] for the sham-operated animals was 22.4%. Sympathectomy significantly reduced this heterogeneity in the anterior cortex through a reduction in the number of low O2 saturation veins (coefficient of variation 11.7%). Blood flow and O2 consumption in the anterior cortex were not different between groups. The effects of sympathectomy in the posterior cortex were similar to those in the anterior cortex. However, sympathectomy did not alter any measured variables in the medulla. Thus, bilateral superior cervical ganglionectomy reduced the heterogeneity of cerebrocortical venous O2 saturation by reducing the number of low O2 saturation veins in the rostral part of the brain.