Italy, extending from 37 degrees to 46 degrees North latitude is usually classified as a medium risk area for Multiple Sclerosis (MS). However, the results of prevalence studies carried out in Italy indicate ratios from 7.2 to 65.3/100.000. The difference between these prevalence figures may be explained in part by methodological and local regional problems; however real differences from area to area cannot be excluded. The Section of Neuroepidemiology of the Italian Society of Neurology organized a Multicenter Study of the Incidence of Multiple Sclerosis in Italy in January 1982. The period selected was 1 January 1971-31 December 1980. 14 different centers have participated in the study, each investigating one area. The aims of the study are to evaluate incidence of MS in different areas of Northern, Central and Southern Italy and to investigate the effects on the risk of some variables (latitude, altitude, migration, socio-economic and urban-rural factors). The design of the study and the methodological problems are considered in this paper.