A longitudinal study of 266 randomly selected nondiabetic Nauruans [215 with normal tolerance and 51 with impaired glucose tolerance (IGT)] over 6 yr showed that deterioration in glucose tolerance status had occurred in 61 subjects. Of the subjects with initially normal tolerance, 34 (16%) progressed to IGT and 14 (6.5%) progressed to diabetes. Thirteen of the subjects with IGT (25%) progressed to diabetes. Subjects were examined in 1975 through 1976, and follow-up examinations were performed in 1982. After age, a high 2-h plasma insulin response to a glucose load was the factor most predictive of progression from normal tolerance to both diabetes (P less than .001) and IGT (P less than .01). Both a high 2-h glucose level and greater obesity independently predicted progression from IGT, and a diminished 2-h insulin response just failed to significantly improve the model (P less than .06). The negative parameter of the insulin response associated with deterioration from IGT differed significantly (P less than .01) from the positive-parameter estimate of the response associated with progression to diabetes from normal tolerance (P less than .01), implying a qualitative difference between these nondiabetic subgroups. The use of a glucose-insulin interaction term to predict progression to diabetes for all nondiabetic subjects confirmed this difference; this term's addition improved the model (P less than .01), and progression to diabetes was associated with a high insulin response for 2-h glucose less than 7.8 mM but a low response for 2-h glucose greater than 7.8 mM.