The T-cell receptor V beta repertoire expressed by Sezary cells was determined in a series of 16 patients whose samples have been shown to contain a majority of tumor cells. By using anti-V beta monoclonal antibodies, polymerase chain reaction analysis of expressed V beta, and, in selected cases, nucleotide sequencing, we have shown that the expressed V beta segments belong to five V beta families (V beta 5, V beta 6, V beta 8, V beta 13, and V beta 18), which contain a large fraction of the T-cell receptor V beta repertoire and do not share significant similarities in complementary determining region 4. V beta segments from these five families were also found to be strongly expressed by CD4 + CD7- peripheral blood cells obtained by fluorescence-activated cell sorting from two healthy donors. The diversity of the V beta repertoire expressed by Sezary cells appears to be similar to that expressed by circulating non-neoplastic T cells. These data do not support the hypothesis that a common superantigen is involved in the initiation of this form of cutaneous T-cell lymphoma.