Although some information is available regarding immune activation in familial Mediterranean fever (FMF), little is known about either peripheral blood T cell activation marker expression or the T cell proliferative response to phytohaemagglutinin (PHA). In the present study, we aimed to investigate the percentages of peripheral blood lymphocyte subsets, T cell expression of cellular activation markers (CD25, CD69, HLA-DR), the T cell response to PHA and serum levels of soluble interleukin-2 receptor (sIL-2R) and interleukin (IL)-10 in patients with FMF. Forty patients with FMF were enrolled into the study. Control groups were sex- and age-matched and consisted of 20 healthy blood donors and 15 patients with inactive Behcet's disease. The patients with FMF in an attack period had higher levels of sIL-2R than those in an attack-free period, and also in comparison with both control groups. The levels of sIL-2R were also found to be higher in patients with FMF in an attack-free period than those in both control groups. The mean levels of IL-10 were found to be lower in patients with FMF in an attack-free period than those in an attack period and were also lower than those in the healthy controls. In an acute attack period, the absolute counts of CD3+HLA-DR+, CD4+CD69+, CD8+CD25+ and CD8+CD69+ T cells in peripheral blood samples were also higher than those in both control groups. Both the percentages and absolute counts of CD4+CD69+ T cells in peripheral blood samples of patients with FMF in an attack-free period were slightly but significantly higher than those in the healthy controls. In conclusion, our study indicates that the T cell system is abnormally activated in patients with FMF in both the attack and attack-free period and that decreased IL-10 levels may create a tendency to perpetuate subclinical immune activation in the attack-free period.