Early environmental effects including variation in maternal care, can modify hypothalamic-pituitary-adrenal (HPA) axis function. One of the more overt early effects, involving maternal care, is weaning restraint. In this study the effects of different patterns of weaning, in the rat (Rattus norvegicus), on both adult response to restraint stress and to dexamethasone administration were examined. Animals that as pups experienced a gradual lengthening time of separation from the mother, between 21 and 30 days of postnatal age (completely separated on 30 days), showed lower levels of systemic corticosterone and glutamate in the sensory cortex in response to restraint stress than seen in other groups. These animals also showed greater suppression of corticosterone by dexamethasone than did animals abruptly removed from the mother at 21 days of age. Animals left in the cage with the mother until either 30 or 40 days of age showed the greatest levels of corticosterone and glutamate in the sensory cortex in response to the stress and the least suppression by dexamethasone. These results suggest that changes in maternal contact at time of weaning can influence adult responsiveness to stress.