Satietin, a 50,000 dalton anorectic glycoprotein, was isolated from human serum. Its isoelectric point is 7.0. It contains 14-15% amino acids and 70-75% carbohydrates. Its biological activity survives digestion with proteases and boiling. Satietin is a highly potent anorectic substance. The intra-cerebroventricular administration on 10-20 micrograms satietin suppresses food intake in rats during the first day of feeding after deprivation of food for 96 hours to half of the amount eaten by untreated controls (ID50). The onset of the effect can be detected within 30 minutes, the peak effect is reached within an hour. The effect lasts 24-30 hours. Satietin acts both in intravenous and subcutaneous administration (ID50 = 0.5-0.75 mg/kg) in rats deprived of food for 96 hours. The peak effect is reached within an hour and lasts for 24 hours. In contrast to the anorectic drugs in clinical use and to the endogenous anorectic substances (like cholecystokinin and calcitonin) satietin proved to be highly selective in suppressing food intake. Since satietin is widely distributed in the world of vertebrates, its concentration in the blood is amazingly high, its site of effect is in the central nervous system and it induces satiety without having any other detectable central or peripheral effect, the hypothesis was forwarded that satietin may play the role of a rate limiting blood-borne satiety signal in the negative feed-back of food intake, i.e., serving as the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding.