The effect of chronic uremia on activities of cerebral dihydropteridine reductase (DHPR) and tyrosine hydroxylase (TH) and content of norepinephrine and dopamine was investigated in the male Sprague-Dawley rats. The uremic animals were fed diets containing either 8% or 18% casein ad libitum, and sham-operated pair-fed and ad libitum fed animals were used as controls. There were no significant differences in TH activity between the groups fed the two levels of protein. Uremic rats had lower activity of TH than pair-fed controls, and pair-fed controls had lower activity than ad libitum-fed animals. DHPR activity and norepinephrine and dopamine content did not differ among the groups. Our study suggests that the chronic uremic condition or restricted feeding causes a decrease in brain TH activity which is not mediated by decreased DHPR activity. Further, this decreased enzyme activity does not result in depressed catecholamine content, indicating the presence of a highly regulated mechanism controlling catecholamine levels.