Cimaterol when added to the diets for 3 or 9 wk stimulated whole animal energy expenditure and brown adipose tissue thermogenic activity comparably in genetically obese (ob/ob) and lean mice; however, ob/ob mice fed diets containing 140 or 280 micrograms cimaterol/kcal failed to increase energy intake as much as lean mice. Consequently, the efficiency of energy retention was actually lower in ob/ob mice fed diets containing cimaterol than in similarly treated lean mice. Cimaterol stimulated skeletal muscle gain in ob/ob mice, although at no point did final hindlimb muscle weight of ob/ob mice equal that of lean mice. Hyperinsulinemia was abolished in ob/ob mice fed diets containing cimaterol even though plasma corticosterone concentrations remained elevated. We conclude that cimaterol has greater effects on energy balance and plasma insulin, but not on skeletal muscle accretion, in ob/ob mice than in lean mice.