To examine the effects of leg exercise on insulin absorption from various injection sites, 125I-labelled rapid actin insulin (9 units) was injected subcutaneously into the leg, arm or abdomen of patients with insulin-dependent diabetes before one hour of intermittent leg (bicycle) exercise and on a resting, control day. Insulin disappearance from the leg increased by 135 per cent during the first 10 minutes of leg exercise (P less than 0.05) and remained 50 per cent above resting levels after 60 minutes (P less than 0.02). Leg exercise had no effect on insulin disappearance from the arm, but insulin disappearance from the abdomen was reduced during the post-exercise recovery period (P less than 0.02). As compared to leg injection, arm or abdominal injection reduced the hypoglycemic effect of exercise by 57 per cent (P less than 0.02) and 89 per cent (P less than 0.005), respectively. Leg exercise accelerates insulin absorption from the leg. Arm or abdominal injection avoids this acceleration during leg exercise and reduces exercise-induced hypoglycemia.