We have screened the whole genome for linkage in 40 Italian multiplex families with multiple sclerosis using 322 markers. The GENEHUNTER-PLUS program was used to analyse these data and revealed eight regions of potential linkage where the lod score exceeds the nominal 5% significance level (0.7). No region of linkage with genome-wide significance was identified and none of the markers showed evidence of statistically significant transmission disequilibrium. Overall these results have refined the linkage data relating to this disease in Italians modestly supporting some previously identified areas of interest and helping to exclude others.