A prospective study of 2121 patients in the southeastern United States having no evidence of glaucoma, suspected of having primary open angle glaucoma, having primary open angle glaucoma, or having open angle glaucoma with exfoliation syndrome revealed an overall prevalence of exfoliation syndrome of 1.6% and a prevalence in the glaucoma subpopulation of 6.0%. All but one of the 33 patients with exfoliation syndrome were at least 60 years of age, and the prevalence of exfoliation syndrome in the subgroup of 1000 patients in this age group was 3.2%. Among the patients in this age group who did not have open angle glaucoma, 1.6% had exfoliation syndrome, and this prevalence was significantly less than those reported in studies from other geographic areas.