Existing data on the incidence of multiple sclerosis (MS) in the UK have some limitations. Few studies have reported age- and sex-specific incidence rates of MS, and none of those is based on a large sample of the general population. Further, no published reports have provided age- and sex-specific incidence rates of MS by clinical course from onset. To estimate the age- and sex-specific incidence rate and lifetime risk of multiple sclerosis, we identified all new cases of MS during the period 1993-2000 in the General Practice Research Database, which includes health information on over three million Britons. Based on 642 incident cases, incidence rates of MS adjusted to the world population were 7.2 (95 % CI 6.5, 7.8) in women and 3.1 (95 % CI 2.6, 3.5) in men. The incidence of MS with relapsing-remitting onset was higher in women than in men (incidence rate ratio 2.5, 95% CI 2.1, 3.1), but there were no sex differences for primary-progressive MS (incidence rate ratio 1.1, 95% CI 0.7, 1.8). The estimated lifetime risk from birth of receiving an MS diagnosis was 5.3 per 1,000 in women and 2.3 per 1,000 in men. These results confirm the relatively high incidence of MS in the UK and show marked differences in the sex-specific pattern of MS incidence by clinical course from onset.