Ethanol, morphine, cocaine and amphetamine were examined in place conditioning. After determination of initial preferences, animals were conditioned with ethanol (1 g/kg), morphine (5 mg/kg), cocaine (5 mg/kg) and amphetamine (5 mg/kg) alone or with combinations of these drugs plus naloxone (1 mg/kg). Naloxone prevented the ability of all drugs used to produce a place preference. The reinforcing properties of ethanol and morphine were reduced by sodium nitroprusside at a dose equal to 1/10 of LD50 given before preference testing. Molsidomine (1/10 LD50 and 1/20 LD50) altered the expression of the conditioned place preference produced by ethanol but not by morphine. Results of the present study suggest the involvement of endogenous opioids and probably of nitric oxide in the rewarding actions of drugs of abuse.