Multiple sclerosis (MS) has been reported to be associated with restriction fragment length polymorphism (RFLP)-defined alleles of the T cell receptor (TcR) alpha- and beta-chain genes. One hundred patients with MS, 23 with primarily chronic progressive MS and 77 with relapsing/remitting MS, as well as 100 controls were investigated with RFLP analysis of the V beta 8, V beta 11 and C beta TcR gene segments. No association was found with allelic patterns or, contrary to a previous report (Beall et al. (1989) J. Neuroimmunol. 21, 59-66), TcR beta-chain gene haplotypes. Subgrouping of patients according to clinical form of disease or MS-associated HLA class II alleles also failed to show associations to TcR beta-chain RFLPs. Thus, our results fail to confirm that TcR beta-chain gene haplotypes confer susceptibility to MS.