The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry reclassifies cases according to standardized diagnostic criteria (currently those of Poser et al). A total of 14,441 cases fulfilling the diagnostic criteria had been registered at the most recently completed follow-up by 1 January 1997; 10,851 had onset from 1948 to 1996 and 3560 before 1948. The completeness has formerly been estimated at about 90%, higher for cohorts with older onset and lower for cohorts with onset close to follow-up. The estimated validity of the diagnosis for autopsy cases classified as definite MS in the Registry is 94%. A long-term nationwide Registry has proved to be a valuable instrument for monitoring incidence and prevalence, analysing survival, performing genetic analysis, providing unselected patient samples for clinical analyses, performing case-control studies and prospective studies and estimating the need for treatment and care.