Glucagon (1.7 × 10−9M) stimulated gluconeogenesis, ureogenesis, lactate production, ketogenesis, proteolysis and glycogenolysis in the isolated perfused rat liver. Insulin at relatively low concentrations (10-100 μU/ml.) suppressed these metabolic effects of glucagon. When a molar glucagon:insulin ratio (2.6 or 26) was selected, which partially suppressed the stimulatory effects of glucagon and the inhibitory effects of insulin, a 100-1,000 fold change in insulin and glucagon concentration at a constant glucagon:insulin ratio, did not alter the rate of gluconeogenesis, ketogenesis, ureogenesis, glycogenolysis or lactate production. These results indicate that glucagon and insulin are complete competative antagonists in the perfused liver. This suggests that it is the glucagon:insulin ratio and not the absolute concentration of either hormone that determines their metabolic events in liver.