Epidemiological studies of multiple sclerosis (MS) conducted in the Faroe Islands identified 10 annual incidences per 100,000 in 1945 and 4.5 in the period 1986-2007. The aim of this study was to estimate the annual incidence of onset of MS in the Faroe Islands in the six decades from 1943 to 2002 and during the period 2003-7.All patients diagnosed with MS between 1943 and 2007 were documented. The incidence of MS before 1943 was around 0.2 per 100,000 annually. During the period 1943-62, an annual incidence rate of 4.4 [confidence interval (CI) 2.9-6.1] per 100,000 was observed. During the 20-year period 1963-82, the level declined significantly (p < 0.001) to around 0.6 (0.3-1.5). Thereafter, an increase was seen during the period 1983-2002, evidencing a significant (p < 0.001) sevenfold increase in the annual incidence to 4.6 (3.2-6.2) per 100,000. Subsequently, for the period 2003-7, there was again a decline to 2.4 (2.1-3.3) (p = 0.003). This study confirms that significant variation in the incidence of MS has occurred in the Faroes over time. Because the rate of genetic change within the Faroese population is relatively slow, the study suggests environmental factors as a contributing cause of MS. If only genetic factors for susceptibility were important, the incidence rate should not wax and wane over time, as is observed.