ABSTRACT BRL 35 135, via its active deesterified metabolite BRL 37344, is a potent example of a new group of/3-adrenoceptor agonists that stimulate selectively a novel/3ad-renoceptor that was originally shown to be present in brown adipose tissue in rodents. BRL 35 135 produces a dose-related increase in energy expenditure in rodents and, in genetically obese (ob/ob) mice, a dose of 0.5 mg-kg‘-d’has significant antiobesity activity. This weight loss is entirely due to loss of fat; muscle protein is preserved. In studies in nonobese men, BRL 35 135 (0. 1 mg/kg) increased both resting metabolic rate and the thermic response to a glucose load. BRL 35 135 is effective in improving glucose tolerance in genetically obese (ob/ob) mice and obese Zucker (fa/fa) rats at doses that have no significant antiobesity activity. The improved glucose tolerance is the result ofsignificant improvement in insulin sensitivity. In lO-d studies in obese and diabetic patients, BRL 35135 produced improvements in glucose tolerance and insulin sensitivity. Am J Clin Nuir 1992; 55: 252S-7S.