Intensive search of all cases of MS occurring in the Sardinian commune of Macomer since 1912 indicated that MS was absent up to the early 1950s. All 13 ascertained cases had clinical onset in the years 1952-1981. During this period, the average annual incidence was 4.8 per 100,000; the highest incidence was found in the period 1957-1961, slowly decreasing up to 1981. MS was probably introduced after 1945, when the centuries-old isolation of Macomer ended and the native population came into contact with individuals from high- and medium-risk areas.