The distribution of gamma delta T cells was determined in peripheral blood of 50 patients in acute relapse of clinically definite multiple sclerosis (MS), 8 patients with primary progressive MS, 26 patients with inflammatory neurological disease (IND), 33 patients with non-inflammatory neurological disease (NIND) and 31 healthy subjects. Paired cerebrospinal fluid samples were obtained from 37 patients with relapsing-remitting MS, 2 patients with primary progressive MS, 14 with IND and 18 with NIND. The monoclonal antibodies pan-alpha beta TCR, TCR delta 1, delta TCS1 and anti-delta V2(a) which identify alpha beta T cells, gamma delta T cells, V delta 1, and V delta 2 gene products respectively, were used to define the T cell receptor repertoire. gamma delta T cells expressed as a percentage of CD3 + lymphocytes were lower in MS CSF compared to NIND CSF (3.4% +/- 0.5 versus 7.3% +/- 1.4; p < 0.001). This was due to a lower percentage of both V delta 1 + (1.3 +/- 0.3% versus 3.3 +/- 0.5; p < 0.001) and V delta 2 + (1.9 +/- 0.3 versus 4.6 +/- 0.8; p < 0.001) subsets in MS CSF. Peripheral blood levels of gamma delta T cells were normal in each study group. CD45RA expression was increased on gamma delta T cells in CSF of each patient group when compared with the paired blood samples. These results suggest that V delta 1 + and V delta 2 + gamma delta T cells with altered CD45 expression are reduced in CSF of patients with established MS. This finding may be related to sequestration or apoptosis of gamma delta T cells within active MS lesions.