In this study, we have evaluated the effect, over approximately 14 yr, of differences in baseline degree of hyperinsulinemia on weight gain in 647 healthy, nonobese factory workers. The subjects were divided into 4 quartiles, on the basis of their plasma insulin response to an oral glucose challenge, in 1981. At that time, the mean (+/-SD) plasma insulin concentration, 2 h after the glucose challenge, varied from 18+/-5 to 106+/-42 microU/mL. Despite this approximate 6-fold difference in plasma insulin response at baseline, the weight gain over the period of observation was similar in all quartiles, with mean (+/-SD) increments (kg) of 1.8+/-5.1, 1.6+/-5.3, 2.3+/-5.2, and 2.3+/-5.7, going from the lowest quartile to the highest quartile, in terms of insulin concentration. Furthermore, when the population was considered as a whole, there was no correlation between baseline degree of hyperinsulinemia and change in either absolute (r = 0.004) or percent (r = 0.003) weight gain. Finally, there was no difference in the number of individuals who gained more than 4.5 kg, as a function of their baseline insulin response. Consequently, we conclude that 6-fold differences in plasma insulin responses to glucose do not predict weight gain in a healthy, nonobese population.