The development of antioxidant enzymes in rat brain and reaggregation cultures of fetal brain cells was studied from embryonic day 15 to postnatal day 45. Both in vivo and in culture, the copper-zinc superoxide dismutase activity first increased and then decreased with age, whereas the manganese superoxide dismutase activity increased throughout the period. Catalase showed a maximum activity at day 5 after birth, thereafter decreasing to adult level around day 30, both in vivo and in culture. The glutathione peroxidase activity increased from the first week after birth and reached adult level at day 45. In culture, the activity of this enzyme was slightly lower. The good correlation between the development of the antioxidant enzymes in vivo and in culture suggests that reaggregation cultures might be a valuable system for studying defense mechanisms against free radicals in the brain.