Rats that consume a high-protein diet are hyperactive, hyperresponsive to noxious stimuli, and demonstrate elevated basal arousal levels. Although the mechanism involved in dietary protein-induced changes in behavior is unclear, it may involve many changes including abnormal dendrite morphology in the brain. Three groups of rats were pair-fed with isocaloric diets containing 8%, 20% and 50% casein for 4 weeks. Their brains were processed for examination of dendritic spine densities in the frontal, parietal, and entorhinal cortices, the striatum, and the septum. Animals on the 50% casein diet showed increased spine densities in all areas investigated (P less than 0.05), compared to the animals on normal (20%) casein. In contrast, animals maintained on the 8% casein diet showed increased spine densities (P less than 0.05) only in the striatum and entorhinal cortex, and exhibited normal densities in the frontal and parietal cortices, and the medial septum.