We reviewed the records of all patients with optic neuritis (ON) in Olmsted County, Minnesota, identified through the comprehensive records-linkage system at the Mayo Clinic, and identified 156 ON patients from 1935 to 1991 who had onset of the disease while residing in Olmsted County (incidence cases). Poisson regression analysis revealed that age, gender, and calendar year were associated with incidence. The annual age- and sex-adjusted incidence rate was 5.1 per 100,000 person-years from 1985 to 1991. On December 1, 1991, 128 patients with a documented history of ON resided in Olmsted County (prevalence cohort). The age- and sex-adjusted prevalence rate per 100,000 was 115. The average length of follow-up for the incidence cohort was 13.2 years. Life table analysis showed that 39% of the 95 patients with isolated ON in the incidence cohort had progressed to clinically definite multiple sclerosis (MS) by 10 years of follow-up, that 49% had by 20 years, 54% by 30 years, and 60% by 40 years. There was no difference in the risk of developing MS between men and women. The presence of venous sheathing (p = 0.044) and evidence for recurrent ON (p < 0.0001) were associated with an increased likelihood of developing MS. The estimated 25-year survival rate was 88.3% +/- 5.8% for the incidence cohort with isolated ON, compared with 83.9% for the general US population of similar age and sex.