The potential for synthesis of prostaglandin E2 (PGE2) in cerebrum (CC), cerebellum (CM), mid-brain (MB) and brain stem (BS) was measured in 1 and 15 month old male F344 rats fed diets containing 0, 30, or 200 IU vitamin E (-E, E, +E, respectively) and 0.0, 0.1, or 0.2 ppm selenium (-Se, Se, +Se, respectively) for 8 or 20 weeks. Regardless of dietary treatments, the rank order of PGE2 synthesis was CC greater than CM greater than BS = MB in the young rats; CC greater than MB greater than BS = CM in the old rats; and CC greater than MB greater than BS greater than CM in the aged rats. PGE2 synthesis in all brain regions were significantly influenced by dietary treatments except CC. -E diets increased and +E diets decreased PGE2 production. Young rats were most susceptible to PGE2 alteration by vitamin E deficiency while old rats responded most markedly to supplementation. All brain regions showed decreases in their capacity to synthesize PGE2 with age, except MB where the opposite effect was seen. Dietary Se treatment had a minimal role in PGE2 synthesis in gross anatomical regions of brain. The degree to which PGE2 synthesis is affected is more dependent on dietary vitamin E level and tissue alpha-tocopherol content than on Se. CM and BS of aged rats appear to require more alpha-tocopherol to maintain steady state levels than other areas, thus the synthesis of PGE2 in these regions could be highly susceptible to alterations in dietary vitamin E.