The purpose of this study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentration of growth hormone (GH) when dietary γ-aminobutyric acid (GABA) treatment was manipulated in hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.5% GABA added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone in the sham-operated rats. However GABA treatment to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that treatment with GABA is likely to increase the concentrations of GH and the rate of brain protein synthesis in sham-operated rats only, not in hypophysectomized rats, and that the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis.