The T-cell receptor repertoire was analyzed in C57BL/6 mice upon infection with helper-free stocks of the pathogenic murine AIDS (MAIDS) defective virus in order to demonstrate if, as previously reported, this virus encodes a superantigen. A polyclonal T-cell stimulation involving T cells expressing multiple V beta subsets occurred within the first week of infection, while late in the disease we could note only a 50% deletion of V beta 5 CD8+ cells. Transfection of the MAIDS virus genomic DNA into fibroblasts and B cells expressing major histocompatibility complex class II molecules failed to show any stimulation of cells expressing the specific V beta (V beta 5) previously reported to respond to MAIDS virus-infected cells. In addition, mice lacking V beta 5 cells did not show any significant decrease in susceptibility to the disease compared with mice expressing V beta 5 and bred on the same genetic background. Our in vivo and in vitro results fail to demonstrate a role for a superantigen encoded by the MAIDS defective viral genome in the pathogenesis of MAIDS.