The effect of exercise on 125I-insulin binding to monocytes was studied in 10 healthy subjects. We found that acute exercise (bicycle ergometer for 3 h) led to a significant increase (36%) in insulin binding to monocytes, which returned to basal levels by 24 h after exercise. The changes in insulin binding were mainly due to an increase in receptor affinity. The increase in insulin binding during exercise correlated with the fall in plasma glucose but not with the decrease in plasma insulin or increase in blood ketones. We conclude that acute exercise increases insulin binding which may contribute to augmented insulin sensitivity associated with exercise.