Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been reported to be involved in vulnerability to alcohol and drug dependence in humans, possibly underlying both addictive behaviour and depression susceptibility. The aim of the present study was to investigate the possible interactions between childhood adverse experiences, depressive symptoms and HPA axis function in addicted patients, in comparison with healthy control. Eighty-two abstinent heroin or cocaine dependent patients and 44 normal controls, matched for age and sex, completed the symptoms Check List-90 (SCL-90), measuring depressive symptoms, and the Childhood Experience of Care and Abuse Questionnaire. Blood samples were collected to determine adrenocorticotropic hormone (ACTH) and cortisol basal plasma levels at 8:00 and 8:30 a.m. Addicted individuals showed significantly higher neglect and depression scores and ACTH-cortisol plasma levels respect to control subjects. Depression scores at SCL-90 in addicted patients positively correlated with plasma ACTH and cortisol values. In turn, plasma ACTH levels were directly associated with childhood neglect measures, reaching statistical significance with 'mother-neglect' scores. Plasma cortisol levels were related to 'father antipathy' among cocaine addicts. These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may have a persistent effect on HPA axis function as an adult, partially contributing, together with genetic factors and other environmental conditions, to both depressive traits and substance abuse neurobiological vulnerability.