Chronic administration of aspirin to obese mice had no effect on energy balance and body composition. In contrast, ephedrine increased energy expenditure by 9% and reduced body weight and body fat by 18% and 50%, respectively: obesity, however, was reduced but not reversed. In the presence of both ephedrine and aspirin, increase in energy expenditure found during treatment with ephedrine alone was doubled, and the obese group lost greater than 75% of body fat: obesity was reversed. These studies indicate that although aspirin administered alone has no influence on energy balance it can markedly potentiate thermogenic properties of ephedrine, effects which led to a normalization of body composition of the obese to that of the lean. Such ephedrine-aspirin mixtures, often found in over-the-counter preparations for asthma and bronchial disorders, could be put to new use as aids for treatment of human obesity.