Long-chain fatty acids are analyzed in tissues from infants whose cause of death was not neurologically related. Total n-3 and n-6 polyunsaturated and n-9 monounsaturated fatty acid amounts increased in the whole forebrain during the prenatal and postnatal periods up to at least 2 years of age. The most abundant brain polyunsaturated fatty acids were docosahexaenoic acid (DHA) (22:6n-3), arachidonic acid (AA) (20:4n-6), and adrenic acid (22:4n-6). In neonates receiving total parenteral nutrition for several days, the DHA/AA ratio was outside the normal range in the liver but within the normal range in the brain. Two other children received total parenteral nutrition for many months, but only the one born at 29 weeks of gestation had a low brain DHA/AA ratio. Another infant, born at 25 weeks of gestation, had been fed milk formulas containing high linoleate/alpha-linolenate ratios for 4 months. This infant had less DHA and a lower DHA/AA ratio in both the brain and the retina than had term infants. These data suggest that preterm infants are especially at risk for the effects of dietary fatty acid imbalances.