Alcohol addiction may induce its dependence through a mechanism involving opiate receptors and opioid peptides. For these reasons, we measured ACTH, beta-lipotropin, and beta-endorphin in the plasma and cerebrospinal fluid (CSF) of 29 alcohol addicts and compared these values with those found in 8 normal volunteers. Although no significant differences existed in peripheral concentrations of the 3 peptides, alcohol addicts had beta-endorphin levels in CSF (mean +/- SE, 29.4 +/- 4.5 fmol/ml) that were 3-fold lower than those of the controls (98.4 +/- 10.5 fmol/ml; P less than 0.001) and ACTH levels 4 times higher than control values (30.0 +/- 1.8 vs. 7.4 +/- 1.1 fmol/ml in controls; P less than 0.001), while no difference was found in beta-lipotropin levels. These results suggest that alcohol addiction is associated with a marked alteration in the CSF content of proopiocortin-related peptides which may play a role in the alcohol-seeking behavior typical of the syndrome.