Stimulation of T cells by superantigenic bacterial toxins is selective for cells bearing particular B chain variable (VB) gene segments of T-cell receptor (TCR). In humans, staphylococcal exfoliating toxin (ExT) and toxic shock syndrome toxin-1 (TSST-1) are known to stimulate VB 2-bearing T cells and staphylococcal enterotoxin B (SEB) does not activate VB 2-bearing T cells. We examined the proliferative response of cutaneous T-cell lymphoma (CTCL) cells to ExT, TSST-1, and SEB. Leukemic VB 2.1-bearing CTCL cells were reactive to ExT and TSST-1, but not SEB. In addition, two leukemia CTCL-VB 2- cell samples (one of which was VB 8) showed no substantial response to ExT. Thus, it was shown that Sezary cells proliferate in response to bacterial superantigens in a manner that is restricted by their VB usage. The addition of interleukin-1 (IL-1) in combination with ExT enhanced the stimulative response of VB 2.1-bearing CTCL cells that were pre-cultured with ExT for 7 d, suggesting that IL-1 can be a co-factor for the stimulation. The present study indicates that the superantigen reaction occurs with CTCL cells and implies a possible involvement of bacterial toxins in the pathogenesis of CTCL.