Recent studies of whole brain in rat pups have shown a marked decrease in DNA synthesis following intracisternal (i.c.) administration of beta-endorphin (BE). This investigation examines DNA synthesis in the cerebral cortex and cerebellum to determine whether the effect shows regional selectivity. Two- to twenty-day-old rats were given a single ic injection of BE, and DNA synthesis was assessed 1 h later. In the cerebral cortex, a region that undergoes major phases of cell multiplication in the immediate pre- and postnatal periods, BE significantly decreased DNA synthesis in 2-day-old rats, and a maximal inhibition was obtained by 4 days of age. In contrast, the cerebellum, a region that grows predominantly after birth, showed less sensitivity to BE during the early postnatal days, and a maximal effect was not attained until 10 days of age. While at 15 days of age the inhibition began to diminish in the cortex, a maximal effect was still seen in the cerebellum. Naloxone prevented the response in both brain regions, indicating the participation of opioid receptors. These results indicate that CNS BE is apparently able to alter DNA synthesis throughout the brain, with the greatest sensitivity occurring in those regions with highest mitotic rates at the time of exposure to BE.