Here we investigated the nature of cutaneous T cell lymphoma (CTCL) cells lacking surface CD3. A large number of CD3- CD4 T cells were found in the peripheral blood and lesional skin of a patient with Sézary syndrome, which is a variant of CTCL. Southern blot analysis revealed that a clonal rearrangement of T cell receptor (TCR) genes was detected in the separated CD3- CD4 cells, whereas CD3+ CD4 cells showed no clonal rearrangement, indicating that the CD3- CD4 cells represented CTCL cells. However, the CTCL cells expressed TCR with a particular Vbeta apart from CD3. The CTCL cells showed significant responses to staphylococcal enterotoxins (SEs) in vitro, although they hardly responded to phytohaemagglutinin, Mycobacterium tuberculosis antigen, and alloantigen. They required antigen-presenting cells (APC) to respond to SEB. Blocking analyses with MoAbs revealed that they recognized SEB through TCR depending on HLA-DR and intercellular adhesion molecule-1 (ICAM-1). Taken collectively, these results indicate that the CTCL cells lacking surface CD3 could proliferate in response to bacterial superantigens, whereas the responses to conventional antigens were generally suppressed. These results also implied that CTCL could be exacerbated by bacterial infection.