The aim of the present series of experiments was to investigate the hormonal counterregulatory response to insulin-induced hypoglycemia in trained and nontrained healthy individuals. Five endurance athletes and six controls were administered intravenous insulin infusion at a rate of 0.15 U/kg/h until plasma glucose reached 50 mg/dL. The mean duration of the infusion in the trained and nontrained subjects corresponded to 18.6 and 26.3 minutes (P less than .01), suggesting that the former were characterized by an increased insulin sensitivity. Plasma glucose levels were similar in the two groups at the end of the insulin infusion, as well as during the postinfusion recovery period. Forty-five minutes after the end of the infusion, plasma glucose levels were not significantly different from the preinfusion levels in the two groups. During this period of glycemia recovery, the increases in plasma glucagon, epinephrine, norepinephrine, and growth hormone were at least 50% lower in the trained than in the nontrained subjects. The increase in heart rate and oxygen uptake during the same period of time was significantly higher in the trained subjects. To determine whether this reduced hormonal response to hypoglycemia was due to reduced insulin levels or to an increased sensitivity to counterregulatory hormones, we investigated the effect of epinephrine on plasma glucose in two other groups of trained and nontrained subjects. In response to a constant epinephrine infusion of 0.01 or 0.1 micrograms/kg fat-free mass (FFM)/min, plasma glucose levels increased similarly in the two groups. In conclusion, these results indicate that trained subjects are characterized by a normal recovery from hypoglycemia despite a reduced response of counterregulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS)