The effects of tolbutamide, glipentide and glibenclamide on the utilization of glycerol in adipose tissue from fed rats was studied. Glipentide and glibenclamide reduced the production of glycerol, inhibited the uptake of 1- 14 c glycerol and inhibited the conversion of 1- 14C glycerol to 14 co2 and 14cglyceride-glycerol. Tolbutamide had less of an effect on the parameters studied;only at a high concentration (lmg/ml) did it reduce the formation of 14 C-glycerideglycerol. The differences between the effects of sulfo nylurea compounds versus modulators of intracellular cyclic-AMP levels (insulin, epinephrine, theophylline) on lipid metabolism is pointed out. The data support the possibility that sulfonylureas might act as uncoupling agents in adipose tissue.