Gamma-hydroxybutyric acid, an endogenous compound present in mammalian brain and supposed to be a neurotransmitter or neuromodulator, has been shown to affect several aspects of dependence from some drugs of abuse. It has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. The aim of this study was to investigate whether gamma-hydroxybutyric acid possesses rewarding properties by means of conditioned place preference and intravenous self-administration paradigms. In the present study, gamma-hydroxybutyric acid induced conditioned place preference in rats, was intravenously self-administered by drugnaive mice, and altered cocaine intravenous self-administration in rats. Although to date the physiological role of this compound still remains unclear, there is no doubt that gamma-hydroxybutyric acid, in addition to its proved effect on alcohol and opiate dependence, possesses reinforcing properties of its own and may interfere with the neurochemical events in the rewarding effects produced by psychostimulant drugs. Our investigation points out the abuse liability of this drug, suggesting the use of particular precaution in handling gamma-hydroxybutyric acid as a clinically useful drug.