The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FAA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains, although the rate of decrease of SA with increasing time after injection was different in the two strains. SA of the lysine in cerebral cortical protein increased in both strains with time, but did so more rapidly in the Sprague-Dawley strain. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. However, specific incorporation of lysine into the cerebral gray cortical protein in control animlas was essentially similar in both strains. Despite the similarity in specific incorporation of lysine into brain protein in both strains of control rat, morphine treatment caused a much more marked inhibition of incorporation of lysine in the Wistar rats. Thus, it is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats.