Acarbose is an alpha-glucosidase inhibitor which reversibly and competitively inhibits the digestion of oligo- and disaccharides at the brush border of the small intestine. This study evaluates the preventive and therapeutic properties of acarbose in the treatment of obesity. Dose-response experiments were performed during repeated sucrose loads in man in order to investigate the effects of acarbose on plasma insulin and blood glucose levels. After titration of efficient doses, a long-term tolerance test of acarbose was undertaken in a small pilot study. Finally, the relapse preventing effect of acarbose was tested during double-blind cross-over conditions in 24 weight reduced obese women. In growing Sprague-Dawley rats, the effects of acarbose on body weight, lipid depots and adipose tissue cellularity were tested during pair-feeding and ad libitum conditions. Such effects were also studied in adult ad libitum-fed rats. Blood glucose, plasma insulin, body fat, depot lipids as well as fat cell weight and number were determined with established techniques. During a sucrose load, acarbose reduced insulin in a dose-dependent fashion. Glucose was also reduced, but not dose-dependently and only to a moderate extent. During a 200 g sucrose load, 400 mg of acarbose did not necessarily result in a maximal reduction of the insulin response while the glucose response was maximally inhibited after 100 mg. Acarbose reduced the relapse rate after weight reduction. No serious side effects were observed. Flatulence and meteorism occurred frequently. In growing rats, acarbose retarded the development of body weight and of lipid depots not only during pair-feeding conditions but also in ad libitum-fed animals eating considerably more than their controls. The spontaneous food consumption was increased by acarbose also in adult rats but in these animals neither body weight nor lipid depots were significantly reduced by acarbose. It is concluded that acarbose induces a carbohydrate malabsorption. Insulin levels are reduced not only via a decreased glycemic stimulus but also by interference with other insulin releasing mechanism(s). Acarbose is the first drug ever tested with long-term relapse reducing effects after weight reduction. Animal experiments suggest that acarbose may be of value in the prevention of obesity, particularly since the drug retards lipid accumulation also during ad libitum-feeding.