The TREC content of CD4+ T cells in these patients was heterogeneous (n = 35). However, two groups of patients could be defined: group 1 (TREC rich), similar to healthy controls (n = 17); group 2 (TREC poor), close to active disease (n = 19). No conventional clinical parameter such as age, sex, disease duration, remission duration, treatment, clinical scores or rheumatoid factor could explain this difference. However, age at disease onset was significantly distributed between these two groups (P = 0.021) and correlated with a familial maternal history of RA. IL-7 is essential to thymic T-cell development and to T-cell activation in the periphery. We found large variations in IL-7 circulating levels between RA patients in remission (n = 57). There was a positive correlation between the circulating levels of IL-7 and the TREC content (r = 0.701, P < 0.0001), suggesting that recovery of thymic activity was limited by the availability of IL-7. We investigated T-cell responses to mitogen, antigen, recall antigen and IL-2 in patients with high and low levels of circulating IL-7 (n = 5 for each group). Low levels of IL-7 were associated with hyporesponsiveness to all stimuli, which could be overcome by adding IL-7 to the cultures. In contrast, high levels of IL-7 were associated with optimal responses to all stimuli including recall antigen and were not greatly ameliorated by supplementing IL-7.