Dose-dependent, amphetamine-induced reductions in protein synthesis were determined in vivo by measuring [3H]lysine incorporation into trichloroacetic acid precipitated protein in homogenates prepared from different regions of the brain or liver. Low-to-moderate doses of amphetamine (1-5 mg/kg) decreased striatal protein synthesis whereas higher doses (10 mg/kg) reduced it in the cerebral cortices, cerebellum, and remaining portions of the cerebrum, as well as in the striatum and liver. Reductions in regional brain protein synthesis occur following amphetamine treatment in relatively low doses known to change various aspects of physiology and behavior.