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 <001) and IGT (P < 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 <.06). The negative parameter of the insulin response associated with deterioration from IGT differed significantly (P <.01) from the positive-parameter estimate of the response associated with progression to diabetes from normal tolerance (P <.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 <.01), and progression to diabetes was associated with a high insulin response for 2-h glucose <7.8 mM but a low response for 2-h glucose >7.8 mM.