The present study attempted to establish whether long term abstinence from alcohol restores the stimulatory effects on GH secretion of gamma-aminobutyric acid (GABA) and gamma-hydroxybutyric acid (GHB) that are absent during the first month of alcohol withdrawal. Six 4-year abstinent alcoholic subjects - already tested with GHB 4 years earlier, and seven age- and weight-matched normal controls, were tested p.o. with 800 mg sodium valproate (a drug that enhances endogenous GABA activity), 10 mg baclofen (a GABA B receptor agonist), 25 mg/kg body-weight GHB, or a placebo. The blood samples for growth hormone (GH) assay were taken every 30 min for the next 150 min. Placebo administration did not modify GH secretion in any subject. All drugs induced a significant increase in serum GH levels in normal controls. GH secretion in abstinent alcoholics did not change after baclofen or sodium valproate administration, whereas the GH response to GHB was similar to that observed in normal controls. The data confirm previous observations which suggest that different neuroendocrine mechanisms underlie GABA and GHB control of GH secretion. The data also indicates that the GHB - but not the GABA-stimulated pathway returns to normal in alcoholics after 4 years abstinence.