The peripheral blood of patients with rheumatoid arthritis (RA) contains oligoclonal gamma/delta T cell populations which may contribute to the pathogenesis of the disease. To investigate whether there is persistent gamma/delta T cell oligoclonality in RA peripheral blood, we screened polymerase chain reaction-amplified T cell receptor (TCR) cDNA, derived from peripheral blood mononuclear cells (PBMC) of four RA patients, with sequence specific oligonucleotides (SSO). The SSO used were specific for TCR variable (V) delta 1, V delta 2 and V gamma 9 transcripts comprising V-joining (J) junctions found over-represented in PBMC of the same RA patients, when bled up to 3 years previously. The dominant transcripts were expressed in the new PBMC samples, although in most cases at a lower frequency than was originally detected. In one patient there was almost 100% oligoclonality of V gamma 9-(N)-J gamma 2 junctional region sequences among the V gamma 9 cDNA clones, progressing from 55% oligoclonality in 15 months. These results indicate the persistence of clonally expanded gamma/delta T cells in the peripheral blood of RA patients. Whether this reflects continual endogenous or exogenous antigenic stimulation remains to be investigated. The findings presented in this report may have important therapeutic implications in view of the potential for immuno-intervention for the treatment of human autoimmune disorders, like RA.