Multiple sclerosis (MS) is a demyelinating auto-immune disease of the central nervous system with a suspected genetic component. Previous publications have demonstrated that MS susceptibility is influenced by Major Histocompatibility Complex (MHC) genes and recent studies have focused on additional susceptibility genes. The accumulation of activated T-cells in demyelinating MS lesions, the possible auto-immune mechanism of this disease and the functional relationship between MHC and T cell receptor (TCR) molecules support the hypothesis that TCR genes are good candidates to influence MS development. Published results in this domain are conflicting and still a matter of controversy. In the present study we analysed the influence of V beta, C beta, P lambda G3 and V gamma gene polymorphisms defined by Restriction Fragments Length Polymorphism (RFLP) on 48 pairs of monozygotic and dizygotic twins with at least one of each pair affected, and also in 63 unrelated MS patients for V gamma gene polymorphism. These results have been compared with those in the non affected twins and with data from a control group (Beall et al., 1989) regarding C beta and V beta polymorphisms and with a local control population for V gamma. No significant correlation between C beta, V gamma or P lambda G3 polymorphisms and MS was found, only a non significant tendency to reduced P lambda G3 allele sharing among dizygotic non concordant twin pairs was observed. However one V beta 11, 25 kb allele and a haplotype defined by V beta 11 and C beta alleles showed a correlation with MS susceptibility of borderline significance.(ABSTRACT TRUNCATED AT 250 WORDS)