The important role that neural tissue fatty acid composition plays in neurodevelopment and various pathological states is increasingly recognized. However, there are limited data regarding the fatty acid composition of normal human brain at various ages. The purpose of this study was to describe human cerebral cortex fatty acid composition from ages 2 to 88 years. The relationship between cerebral cortex and erythrocyte fatty acid composition was also investigated. Samples of frontal cerebral cortex and of erythrocytes were obtained from 58 human subjects on whom autopsies were performed. The mean age of subjects was 40 +/- 29 years, with a range of 2 to 88 years. The fatty acid composition of tissues was determined, and linear regression models were used to describe the relationship between age and the fatty acid composition of cerebral cortex and erythrocytes. The data were bilinear, with changes occurring after the approximate age of 18 years. Therefore, the cohort was divided into subjects with ages < or =18 and >18 years. In the younger group, the polyunsaturated fatty acids generally decreased with age, with the exception of 22:6n3, which demonstrated a significant increase. The level of mono-unsaturated fatty acids, in contrast, generally increased to the age of 18 years. Several of the polyunsaturated fatty acids also decreased with age in the older cohort, particularly 20:4n6. The levels of 18:2n6, however, increased significantly with age in the older cohort. Among subjects < or =18 years of age, there was no significant relationship between cerebral cortex and erythrocyte fatty acid levels. In the older cohort, there was a significant relationship between brain and erythrocyte levels for several fatty acids, particularly 16:0. These data demonstrate that levels of cerebral cortex fatty acids change from early childhood through late adulthood, and indicate that the levels of several erythrocyte fatty acids may be useful in predicting brain fatty acid levels in adults.