The frequency of multiple sclerosis in Transylvania was determined for the period 1959 to 1969. The prevalence per 100,000 population on January 1, 1970, based on 925 accepted cases was 25.6; the average annual incidence and mortality were 2.0 and 0.8, respectively. A major north-south drop in the frequency of multiple sclerosis in Europe appears to occur across Romania, whereas a major west-east drop may occur to the west of Romania, perhaps across Austria or Hungary. Using total prevalence in Transylvania to estimate expected frequency in each district, we observed frequency to be significantly higher in two and significantly lower in another two districts. This variation was analyzed in relation to the distribution of familial cases, medical facilities, climate, altitude, urban-rural differences, lead deposits, and foci of arbovirus encephalitis occurring during the study interval.