We investigated the temporal relationships between obesity, weight change and hyperinsulinemia in a population-based 4-year follow-up study of 695 middle-aged, non-diabetic, and normoinsulinemic men. Thirty-eight men developed hyperinsulinemia during the follow-up (fasting serum insulin > or = 12.0 mU/l). In logistic regression analysis adjusting for other risk factors, men with body mass index of > or = 26.7 kg/m2 (highest third) had a 6.6-fold (p = 0.001) risk of developing hyperinsulinemia, compared with men with body mass index of < 24.4 kg/m2 (lowest third). Correspondingly, men with waist-to-hip ratio of > or = 0.95 (highest third) had a 3.5-fold (p = 0.028) incidence of hyperinsulinemia compared with men with waist-to-hip ratio of < 0.90 (lowest third). Weight gain in middle age and weight gain from the age of 20 years to middle age were also associated with increased risk of hyperinsulinemia. Hyperinsulinemia at baseline was not associated with weight gain during the follow-up. This prospective population-based study emphasizes the importance of avoiding obesity and weight gain during adulthood in preventing hyperinsulinemia.