The activity of biosynthetic human insulin (BHI) has been compared with that of pork insulin using the glucose clamp technique in normal subjects. After a baseline period, insulin was infused at 0.02 U/kg/h for 2 h, then 0.032 U/kg/h for 2 h, and finally 0.05 U/kg/h for 2 h. Glucose was clamped at baseline values using a glucose-controlled insulin infusion system (Biostator) and the amount of glucose infused to maintain normoglycemia calculated for each insulin dose for the two insulins. C-peptide levels decreased with both insulins, suggesting suppression of endogenous insulin secretion. Serum insulin levels attained were the same for both insulins. There were no significant differences in either total glucose infused or glucose infused during the last 30 or 60 min at each insulin dose for the two insulins. Intermediary metabolite responses to the infusion of the two insulins were similar. We conclude that in normal human beings, BHI shows identical metabolic activity with pork insulin.