The period of adolescence and environmental factors, such as stress, are important in determining ethanol vulnerability in both humans and rats. Ethanol is a powerful activator of the hypothalamic-pituitary-adrenal (HPA) axis but attenuated responses of the HPA axis to ethanol have been described in populations with a high risk of ethanol abuse. In rats, prenatal stress leads to prolonged stress-induced corticosterone secretion and increases the vulnerability to drugs of abuse, such as amphetamine and nicotine in adulthood and 3,4-methylenedioxymethamphetamine in adolescent rats. The aim of the present study was to assess the impact of a prenatal stress on HPA axis responsiveness to a moderate dose of ethanol (1.5 g/kg i.p.) in adolescent male rats (28 days old). The parameters evaluated were plasma adrenocorticotropic hormone, plasma corticosterone and mRNA expression of HPA axis central markers (mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone and pro-opiomelanocortin). Contrary to prior expectations, our results demonstrate that prenatal stress blunts the HPA axis responsiveness to a moderate dose of ethanol in adolescent rats in spite of similar blood ethanol levels. These data suggest that prenatal stress may have the opposite effect on the response to stress depending on the attributes of the stressor stimulus. They thus raise questions about the possible impact of prenatal stress on the further development of ethanol vulnerability.