In a double-blind drug-placebo cross-over design, naloxone hydrochloride reduced the amount of cigarettes smoked by chronic smokers over a 3 hr period. The number of puffs was reduced by 32%, the weight of the amount smoked by 33%, and the number of trials in which cigarettes were smoked by 30%. The extent of the decreases in smoking was related to the amount of the decrease in the desire to smoke. There were no physiological differences or in side effects between the two conditions, and neither subjects nor experimenters were able to distinguish between the two. These findings are similar to the suppressive effects of naloxone on food, water and ethanol intake in animals and suggest that the endorphins are implicated. A heuristic theory of addiction is presented to explain these diverse effects. Naloxone hydrochloride (NAL) reduces the intake of nonintoxicating positive reinforcers, such as food and water, in animals (1–5), as well as ethanol (6). The reduction does not appear to be part of an abstinence syndrome (3), or of a general suppression of behavior (7), unless massive doses (i.e. 5 mg/kg or more) of the opiate antagonist are used (8). The mechanism for these effects is obscure, although it has been demonstrated that higher levels of Beta endorphin are associated with greater food intake, and that NAL suppresses food intake to a greater extent in genetically obese animals which have higher levels of Beta endorphin than their litter-mates of normal weight (4). Cigarette smoking has often been found to increase corticosteroid levels (9–12), which is considered presumptive evidence that there is an increase in ACTH production. Elevated levels of ACTH are associated with elevated levels of Beta endorphin in man (13–16). Assuming that smoking is another example of a nonintoxicating positive reinforcer, which also releases Beta endorphin because of ACTH release, we administered NAL to chronic smokers, with the expectation that the amount smoked, as well as the desire to do so, would be reduced. However, because of the possible addictive nature of nicotine (17–19), we were not sure whether these effects would be the result of a precipitated abstinence syndrome.