The anti-oxidant enzymes, superoxide disrnutase (SOD), catalase (CAT), glutathione peroxidase (GP), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) were measured in the developing fetal guinea pig brains. Following anesthesia, one group (n=36) of fetal guinea pigs were removed from normoxic mothers and another group (n=36) from mothers subjected to hypoxia (FiO2 7% for 40 min). Fetuses of 30, 35, 40, 45, 50 and 60 days gestation were studied. Fetal brains were removed, homogenized, and analyzed for enzyme activities. The activity of the anti-oxidant enzymes remained constant during 30, 35, 40, and 45 days but increased sharply after 45 days of gestation: CAT from 3.04±0.53 to 5.17±0.75 umoles H2O2/min/mg protein (pr); GP from 25.40±3.50 to 49.66±3.29 nmoles NADPH oxidized/min/mg pr; GR from 18.9±2.30 to 32.54±4.83 nmoles NADPH oxidized/min/mg pr; G6PD from 28.90±4.60 to 38.69±1.39 nmoles NADPH formed/min/rng pr; and SOD from 25.46±4.57 to 32.11±2.85 units/mg pr between 45 and 60 days of gestation. In hypoxic fetal brains at 45 and 60 days of gestation, the enzyme activities were (units as above): CAT 2.67±0.54 and 5.13±1.27; GP 18.80±3.30 and 53.70±2.56; GR 20.60±2.90 and 32.84±3.81; G6PD 24.60±3.90 and 37.97±6.05; and SOD 28.77±4.93 and 27.74±2.21. The data shows that maternal hypoxia leading to fetal hypoxia did not affect the activity of anti-oxidant enzymes of the fetal brain. Although the guinea pig brain is enzymatically mature at term, it is proposed that the brain during early gestation has underdeveloped anti-oxidant enzyme defense mechanisms and is at potential risk from oxidative free radical reactions during normoxia as well as hypoxia. (NIH Grant # 5-RO1-HD 20337).