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SummaryCarbutamide, a sulfonylurea compound capable of lowering blood sugar, did not have an insulin-like action in increasing glycogen deposition of isolated rat hemi-diaphragm. Furthermore, this drug did not produce any enhancement of the insulin effect. In fact, when higher concentrations were used there was a significant inhibition of the insulin effect. This inhibition is somewhat non-specific since it was also observed when sulfadiazine was substituted for Carbutamide. It is suggested that this inhibition, the inhibition of insulinase, and the in vitro reduction of the epinephrine and glucagon response which have been attributed to the sulfonylurea compounds might all be due to a non-specific protein poisoning action of these drugs in higher concentrations.