The effect of chronic diet restriction on amino acids and monoamines in cerebral cortex was studied in young and old male Fischer-344 rats. The effect of restricted feeding (60% of ad lib diet) was compared at 6 and 24 months of age. The results indicate that aging did not significantly alter the levels of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in frontal (FCX), parietal (PCX) and occipital cortices (OCX). On the other hand, the effect of age on serotonin (5HT) was found to be regionally specific. The level of 5HT was 43% higher, while the ratio of 5HIAA/5HT was decreased 26% in OCX of 24 months old animals. In the FCX 5HIAA/5HT ratio was increased 27%. Diet restriction in old rats increased DA level markedly in FCX, and attenuated the age-related increase of 5HT level in OCX. The ratios of 5HIAA/5HT in FCX and OCX of DR animals were maintained at those found in the young ad lib (AL) group. The cortical neurotransmitter amino acids (aspartate, glutamate, gamma-aminobutyric acid, glycine and taurine) were well maintained during aging and dietary manipulation. Age-related reduction of cortical tryptophan and plasma ratio of tryptophan to large neutral amino acids in old animals were attenuated by chronic DR. The results suggest that serotonergic neurons are more susceptible to change during aging than are the catecholaminergic neurons. Diet restriction during the life of the animals appears to protect or attenuate the age-related changes in cortical serotonergic system while FCX dopamine concentrations were dramatically increased.