Endogenous opioid peptides are thought to participate in the phenomena of alcohol tolerance and withdrawal. Since in the pituitary gland, beta-endorphin (beta -EP) and adrenocorticotropic hormone (ACTH) are produced from the same precursor molecule, pro-opiomelanocortin, it may be expected that alterations in plasma ACTH and cortisol levels should parallel changes in plasma beta -EP levels during alcohol withdrawal. The aim of the present study was to investigate the alterations of beta -EP, AC7H and cortisol secretion patterns in alcohol-dependent patients with heavy intake in the early withdrawal period and, if any, whether these changes remained stable on long-term withdrawal. Twenty-two hospitalized male patients (mean age +/- SD: 43.45 +/- 9.22 years, mean daily amount of alcohol +/- SD: 421.59 +/- 116.57 g) who were diagnosed to have alcohol withdrawal and 20 age-matched healthy men (mean age +/- SD: 38.35 +/- 7.63 years) were included in the study. Morning and night levels of plasma beta -ER ACTH and cortisol were measured in the patients during the early (first week) and late (fourth week) withdrawal periods following alcohol cessation, and only once in the control subjects. It was found that both morning beta -EP and morning ACTH levels were reduced during both early and late withdrawals, whereas cortisol levels were increased in early withdrawal and normalized towards the late withdrawal period. The finding that beta -EP deficiency continued despite withdrawal symptoms subsiding in patients suggests that their beta -EP deficiency is independent of the withdrawal syndrome and that reduced beta -EP activity may be a trait contributing to alcohol craving.