The present study sought to investigate the relationship between the HPA axis reactivity to stress, the endogenous opioid system and stress-induced drinking behavior.In the present study, 74 non-treatment-seeking alcohol-dependent subjects were tested under two mood conditions, neutral and stress, in separate testing sessions. Salivary cortisol measurements were obtained following stress induction and during the neutral control condition. Multiple measurements of alcohol intake, latency to access the alcohol cue and craving for alcohol were obtained during cue-availability testing. In addition, 52 of the study subjects were genotyped for the mu-opioid receptor.A blunted cortisol response to stress was significantly correlated with increased alcohol intake following stress exposure compared to alcohol intake during the neutral session. There was not a clear correlation between the change in cortisol in response to stress and the change in latency to access alcohol or alcohol craving in response to stress. Carriers of the Asp40 variant of the mu-opioid receptor exhibited a dampened cortisol response to stress, higher alcohol intake and greater craving in response to stress compared to Asn40 homozygotes, although these differences were not statistically significant.The results of the present study indicate that a blunted biological stress response was correlated with increased drinking in response to stress. The Asp40 variant of the mu-opioid receptor may be associated with this HPA axis hyporeactivity although the small sample size used in the present study did not permit adequate evaluation of this association.