WE used in-situ hybridization to study the effect of acute stress on induction of the immediate early genes (IEGs), c-fos and zif/268, in the rat brain. After one hour of restraint plus intermittent tail shock, messenger RNA (mRNA) levels for both genes were significantly increased bilaterally in the neocortex, particularly in layers IV, V and VI, and in the CA1 region of the hippocampus. This regionally-specific response suggests that IEGs may have a role in the mediation of acute stress responses in the central nervous system.