Daily treatment of Fischer-344 rats for 14 days with the beta 2-adrenergic agonist, clenbuterol, increased gastrocnemius muscle mass and protein content. Coadministration with the beta-adrenergic antagonist, nadolol, significantly reduced these anabolic effects of clenbuterol. Although clenbuterol treatment reduced food intake during the first 4 days, clenbuterol-treated rats were hyperphagic during the second week of drug administration. Nadolol treatment also blocked these effects of clenbuterol on feeding. In a second experiment, in vitro incubation of extensor digitorum longus muscles taken from post weaning food-deprived rats demonstrated decreased release of 3-methylhistidine by clenbuterol-treated rats, suggesting decreased breakdown of myofibrillar protein. Protein synthesis was not increased in vitro in the soleus muscles taken from these rats. These experiments demonstrate that the anabolic effect of clenbuterol is due in part to beta-adrenergic activity and may involve reduced myofibrillar protein degradation. These results appear to have direct application to nutrition and protein repletion in various catabolic diseases.