Zucker fa/fa rats exhibit glucose intolerance in comparison with lean Fa/? littermates. A single acute dose of BRL 26830 (2.9 mg/kg p.o.) improved glucose tolerance in Fa/? littermates but exacerbated glucose intolerance in the fa/fa rats. This latter effect occurred in spite of an increase in the plasma insulin concentration. Chronic treatment of Zucker fa/fa rats with BRL 26830 (2.9 mg/kg) for 24 days or more produced a significant reduction in the area under the glucose tolerance curve. In addition, the glucose decay rate (k%) following the administration of insulin intravenously was significantly increased in the BRL 26830-treated rats suggesting that tissue insulin sensitivity was increased. Glucose turnover measurements show that chronic treatment of Zucker fa/fa rats with BRL 26830 produced a significant increase in the rate of glucose utilization integrated over a 3 hr period, but this increase was, in part, off-set by an increase in the endogenous rate of glucose production. The ultimate fate of the extra glucose that is metabolized is not known but it is suggested that it might be used to support the thermogenic response that is also activated by BRL 26830.