Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), is produced peripherally by gastric and hepatic alcohol dehydrogenase (ADH) and centrally by brain catalase. Experimental evidences suggest that ACD contributes to the positive motivational properties of ETOH. Thus, to investigate the role of ACD in the motivational proprieties induced by ETOH, we decided to study the ability of intragastrically administered EtOH, ACD and EtOH-derived ACD to induce conditioned place preference (cpp) in rats.We showed that a competitive inhibitor of ADH, 4-methyl-pyrazole (4-MP), and a selective ACD-sequestrating agent, D-penicillamine (DP), administered intraperitoneally, before the intragastric administration of EtOH, reduces EtOH-induced cpp. Instead ACD-induced cpp was unaltered by 4-MP administration and prevented by DP. Moreover, thiol products, such as the amino acid cysteine, are known to be effective ACD-sequestering agents. Cysteine, a non essential amino acid, in fact, is able to covalently bind ACD thereby forming a stable compound. Lastly, to analyze the specificity of three drugs, we also investigated the effect on morphine-induced cpp. Our results suggest that intragastric ETOH, ACD and ETOH-derived ACD exert similar motivational properties suggesting that ACD plays a key role in the motivational properties of ETOH as well as in its abuse liability.