The search to identify HIV-associated molecules with superantigenic properties has focussed on demonstration of T cell receptor V beta subset-specific perturbations in HIV-infected patients. In this report, the V beta repertoire of two HIV patients was studied in lymph nodes, where HIV-1 replication is the most intense, and compared to the repertoire found in peripheral blood. Use of this fully MHC-compatible system has allowed identification of a small, partly overlapping set of V beta determinants which appear significantly perturbed in HIV-1 infection. These results are consistent with the presence of an HIV-associated superantigen.