A new technique of programmed intravenous insulin infusion at a series of decreasing rates has been used to imitate the magnitude and time course of biological responses obtained by the subcutaneous route. Groups of normal rats prepared with indwelling venous cannulae were injected subcutaneously with soluble porcine insulin, 0.4 U/kg. The pattern of the resulting hypoglycaemic response was subsequently matched by a 2-hour intravenous insulin infusion at rates decreasing stepwise from 0.3 to 0.05 U kg-1h-1. The total amount of insulin infused intravenously was only 50% of that required subcutaneously. In addition, subcutaneous or intravenous infusions of insulin at 0.05 U kg-1h-1 were given to two groups of rats from the same batch. When both infusions were continued until plateau responses were reached, a significantly greater lowering of plasma glucose was caused by the intravenous route. These results suggest that when insulin is given subcutaneously significant inactivation of the insulin occurs at or near the injection site.