In seven insulin-dependent diabetic subjects the disappearance rate of 125I-labelled short-acting insulin from injection sites in the abdominal wall was 86% greater than from the leg (P less than 0.005) and 30% greater than from the arm (P less than 0.05). Absorption from the arm was 40% greater than from the leg (P less than 0.05). The postprandial rise in plasma glucose concentration varied inversely with the rate of insulin absorption and was 30 to 50 mg/dL less after abdominal than after leg injection; the glycemic response after arm injection was intermediate between that after leg and abdominal injection. These results indicate that changing the insulin injection site from the leg to the abdomen or arm accelerates the absorption of insulin and diminishes the postprandial rise in plasma glucose. Varying insulin injection sites within the same anatomic region rather than between different regions may diminish daily variations in insulin absorption and in metabolic control in insulin-dependent diabetic subjects.