The disposal of intravenous glucose (%/min ± SE) was markedly delayed in rats anesthetized with 50 mg/kg of intraperitoneal sodium pentobarbital (K=2.14 ± 0.23) compared to conscious litter mates (K=3.95 ± 0.21). There were no differences in fasting plasma glucose concentrations or in the insulin response to administered glucose. Diaphragms and epididymal fat pads removed from anesthetized animals differed in their vitro response to glucose and insulin only by a small (10%), but significant (p < 0.05), decrease in the basal glucose uptake of the muscle tissue. Sodium pentobarbital (0.1 mg/ml) added in vitro inexplicably stimulated insulin-mediated glucose uptake of hemidiaphragms from untreated rats but had no effect on adipose tissue metabolism. The pathogenesis of pentocarbital-induced glucose intolerance in the rat remains to be elucidated. 1 Supported in part by a grant from the Diabetes Association of Southern California.