To elucidate the epidemiology of human T-lymphotropic virus type I (HTLV-I) associated uveitis (HAU), a multicenter case-control study was carried out by the collaboration of university hospitals throughout Kyushu and Okinawa in southwestern Japan where HTLV-I is endemic; two institutions in the non-endemic metropolitan areas of Tokyo and Yokohama also participated. A total of 426 cases of endogenous uveitis were registered during the five-month period between September 1992 and January 1993; the etiology and clinical entity of about half of the cases were definable, and for the remaining half were unknown. Assessment of antibodies to HTLV-I revealed that the group of entity-undefined uveitis cases showed a significantly high seroprevalence when compared with age- and sex-matched controls. Estimate of the risk of HTLV-I provided supportive evidence for its etiologic contribution to a considerable proportion of hitherto undefined isolated uveitis cases. The prevalence of HAU thus defined was found to correspond to the seroprevalence in the relevant areas. Occasional cases were found among residents in the nonendemic metropolitan areas who had moved from the endemic areas.