1. Thirty-three drugs known to stimulate the sympathetic nervous system have been screened for thermogenic properties. The results presented are for seven of them.2. The drugs were tested in five animal models of obesity (genetic (mice and rats), hypothalamic (mice) and dietary (mice and rats)) as well asin leanmice. Energy-balance studies were undertaken using thecomparative-carcass technique as well as by measurement of daily oxygen consumption.3. All seven drugs in obese animals tended to reduce body-weight and fat without loss of body protein: they acted by increasing metabolic rate without increasing food intake. They were much less effective in lean animals. These findings lend support to the concept that obesity is due to a diminished activity of the sympathetic nervous system.4. Differences in the effectiveness of the drugs are discussed in relation to differences between the animal models of obesity. Ephedrine and tranylcypromine were found to be the most effective drugs in this series of experiments and a prima facie case is made for human clinical trials.