The glucagon effect (150 microgram/3 hrs) on isolated oleate-perfused (1.67 microEq/min) liver has been determined both in fa/fa obese hyperlipemic Zucker and diet-induced hyperlipemic Sprague Dawley rats and in the respective lean strains. Glucagon exerted a normal hypotriglyceridemic effect in hyperlipemic as well as in non-hyperlipemic rats. The ketone body output and the triglyceride liver content were not significantly modified by glucagon. Our data suggest that there is a normal liver responsiveness to the hyolipidemic action of glucagon and, consequently, that there is no glucagon resistance in genetically or diet-induced hyperlipermic rats.