The incidence and prevalence of diabetes mellitus were determined in 3733 Pima Indians aged 5 years or over by periodic examinations over a 10-year period. The examinations included modified glucose tolerance tests and medical record review. The age-sex adjusted prevalence rate was 21.1% (SE = 0.7%). Prevalence was low in childhood and plateaued at 40--50% in adults over 35 years of age. The age-sex adjusted incidence rate of 26.5 cases/1000 person-years (SE = 1.9) is the highest reported diabetes incidence known to the authors. Incidence increased from low levels in childhood to peak at age 40 (males) or 50 (females) and then gradually declined. Diabetes incidence was 19 times that in the predominantly white population of Rochester, Minnesota (95% confidence interval, 16 to 22 times). The high incidence rate was found despite using a more stringent diagnostic criterion than customarily employed, and was shown not be due to biased follow-up of subjects.