In order to establish whether long-term abstinence from alcohol reverses the defective serotonergic and GABAergic controls of growth hormone (GH) secretion affecting alcoholic patients, the 5-HT1D serotonergic receptor agonist sumatriptan and the GABAergic agent gamma-hydroxybutyric acid (GHB) were administered to 12 normal men (32-49 years) and 22 non-depressed male alcoholic subjects (38-52 years) after 1-2 years of abstinence from alcohol. All subjects were also tested with placebos. Furthermore, tests with GH-releasing hormone (GHRH) and L-arginine (which releases GH from somatostatin inhibition) were performed to determine whether GH secretion in response to its major determinants is preserved in alcoholics. Administration of placebo did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and alcoholic subjects when GHRH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan or GHB injection; in contrast, GH secretion was not modified by sumatriptan or GHB administration in alcoholic patients. These data show a persistent selective loss of 5-HT1D receptor and GHB-mediated neurotransmissions in alcoholics that a long-term abstinence from alcohol is unable to restore.