1. Pharmacological evidence indicates that stress induced by brief (14 to 20-day) social deprivation in the rat is associated with an activation of the central preproenkephalin (ENK) opioid system. This study examines the neurochemical evidence that substantiates such an activation. 2. Using a specific ENK complementary DNA probe, ENK RNA levels were measured by dot blot and Northern blot analyses in different brain areas of socially deprived rats. Immunoreactivity to met-enkephalin-derived peptides was also evaluated by radioimmunoassay in the same brain regions. 3. Brief social deprivation increased the levels of ENK RNA and enkephalin immunoreactivity in whole hypothalamus. 4. Our data suggest that this type of stress appears to be associated to an induction of ENK gene transcription in hypothalamus.