When mice were subjected to footshock treatment and subsequently injected with [3H] lysine, the cerebral uptake of [3H] lysine, its incorporation into brain protein and the relative radioactivity (RR = protein radioactivity divided by amino acid radioactivity) were all increased. In the liver, footshocked mice showed decreased free lysine radioactivity, and increased protein radioactivity and relative radioactivity compared to quiet mice. The possibility that ACTH mediated these effects was investigated. The injection of saline had no effect in the brain but partially mimicked the footshock responses in the liver. Injections of ACTH 1--24 mimicked the effects of footshock in the brain, and further augmented the saline-induced effect on the RR in the liver. ACTH 4--10 increased the RR of brain protein, but produced no significant change in brain free lysine radioactivity or in any measure in the liver. Pretreatment of mice with the synthetic glucocorticoid, dexamethasone, did not enhance these effects and diminished the effect of ACTH 4--10 in the brain. ACTH treatment did not alter the profiles of brain polyribosomes. Lysine vasopressin, which is also released during stress, did not alter the incorporation of [3H] lysine into brain or liver protein, except at high doses when it decreased plasma radioactivity. These results suggest that secretion of ACTH at least partially mediates the stress-induced changes of [3H] lysine incorporation into brain and liver proteins, but that it is probably not the only factor involved.