Corticotropin-releasing factor (CRF) and restraint-stress both decrease exploratory behavior in rats and mice. The involvement of pituitary-adrenal hormones in eliciting these behavioral effects was examined using hypophysectomized mice. Forty minutes of restraint decreased exploratory behavior in hypophysectomized mice just as it did in intact animals. Similarly, CRF (50 ng) injected into the lateral cerebral ventricles of hypophysectomized mice decreased exploratory behavior. Therefore, the restraint- and CRF-induced decreases of exploratory behavior are apparently independent of the activation of ACTH secretion from the pituitary. It seems likely that CRF acts intracerebrally to elicit this effect of restraint, especially because a CRF antagonist can reverse the effects of restraint.