The effect of aprotinin on the absorption of regular insulin was assessed in normal man. Ten units of Actrapid insulin were subcutaneously injected together with 1.4 mg aprotinin (i.e., 0.5 ml of Trasylol) or an equivalent volume of physiologic saline (controls) into the thighs of overnight-fasted normal subjects. Aprotinin caused an increase in the rate of insulin entry into the circulation; the absolute amount of insulin that was detected in the circulation during the course of the experiment was also higher. In addition, the onset of the hypoglycemic action of exogenous insulin was significantly accelerated when insulin was administered together with aprotinin. These data suggest that aprotinin increases the absorption rate of subcutaneously injected insulin from its depot into the circulation, possibly by an inhibition of the local degradation of exogenous insulin at the injection site.