The thermogenic effect of an over-the-counter preparation containing 22 mg ephedrine, 30 mg caffeine and 50 mg theophylline was investigated in human volunteers with a predisposition to obesity and also in the lean. The ephedrine/methylxanthines mixture was twice as effective as ephedrine alone in increasing the fasting metabolic rate of both subject groups, and it normalized the reduced thermogenic response to a 1.25-MJ meal observed in those predisposed to obesity. Measurements of 24-h energy expenditure in a respirometer indicate that the mixture had no effect on the daily metabolic rate of the lean, but was effective in causing a significant 8 percent increase in the 24-h energy expenditure of those subjects predisposed to obesity. These studies indicate that relatively mild doses of dietary methylxanthines in combination with ephedrine can raise daily energy expenditure of those predisposed to obesity, mainly by correcting their defective thermogenic response to food. Such ephedrine/methylxanthine preparations could be useful as aids in the treatment of obesity.