OBJECTIVE: To describe a cohort of patients with pars planitis followed at a single tertiary care institution, determine the frequency of multiple sclerosis and/or optic neuritis in patients with this disorder, and calculate gene frequencies of human leukocyte antigen (HLA) class II alleles in these patients. DESIGN: Fifty-three patients with the diagnosis of pars planitis underwent clinical record review or telephone interview for follow-up or both; 32 of these underwent phlebotomy for analysis of HLA class II alleles. MAIN OUTCOME MEASURES: Outcomes included visual acuity, occurrence of multiple sclerosis and/or optic neuritis, and HLA class II gene frequencies. RESULTS: With a mean follow-up of 2 years, approximately 90% of patients maintained a visual acuity better than 20/40 in at least one eye. The most frequently encountered ophthalmic complications included cystoid macular edema, cataract, and epiretinal membrane formation. Of 37 patients with pars planitis who had medical or neurologic follow-up evaluations, 6 (16.2%) developed multiple sclerosis. The HLA-DR15 allele, coding for one of the two HLA-DR2 subtypes, was associated with pars planitis (odds ratio = 2.86, 95% confidence interval = 1.42-5.78, P = 0.004). CONCLUSIONS: A common immunogenetic predisposition to multiple sclerosis and pars planitis may be associated with the HLA-DR15 allele. This association may represent genetic linkage to the HLA-DR locus or a role for the HLA-DR15 gene product in the pathogenesis of both of these diseases.