Three-year-old rats could easily establish a new behavior consisting of reversal of handedness in an instrumental learning test. These old animals acquired the new behavior at the same rate as young adult rats, but did not perform as well. Incorporation of Z 14 C]valine into soluble protein of different parts of the limbic system and cortex cerebri was measured, as well as dye uptake into protein bands on polyacrylamide gel electrophoresis. In the hippocampus, entorhinal cortex, septum, and sensory-motor cortex, and one specific protein fraction increased in synthesis. We also report upon some other specific responses due to the acquisition of the new behavior of the very old rats.