We have shown earlier that CD8+ T cell oligoclonality occurs frequently in normal individuals and general exhibits a very diverse repertoire. In order to investigate the role of CD8+ T cells in MS, we analysed CD8 oligoclonality in 125 patients with MS in varying stages of disease. A multiplex PCR assay for CDR3 length variation was employed to detect oligoclonality in 25 TCRBV segments/families. CD8 clonal dominance was found to be frequent in MS. Comparison of the CD8 T cell repertoire in MS with that in normal controls revealed an increased frequency of oligoclonality involving the TCRBV9, -18 and -23 families. Sequence analysis of the TCRs from these clonally dominant CD8+ cells revealed a high degree of diversity overall. However, we observed one instance of identical TCRBV18 sequences in CD8 cells from two unrelated MS patients. In addition, several TCRs with motifs homologous to those found in MS brain and MBP specific T cell clones in EAE and MS were also detected. Future characterization of the function and specificity of these clonally expanded populations may provide insight into the nature of immune dysregulation in this autoimmune disorder.