The effect of growth of BALB/c C4 preneoplastic and neoplastic mammary lesions on the host T-cell repertoire was investigated. T-cells with specific V beta regions (V beta 2, -6, -8.1-2, -11, and -14) in the T-cell receptors were enumerated in C4 hyperplastic alveolar nodule (HAN)-infiltrating lymphocytes and lymph node cells from both C4 HAN and C4 tumor-bearing mice by flow cytometry with V beta-specific monoclonal antibodies. Growth of C4 HAN and tumor induced selective deletion of peripheral V beta 2+ T-cells. Elimination of V beta 2+ T-cells [7.2 +/- 0.8% (SD) of normal lymph node T-cells] by C4 HAN was biphasic and irreversible. Approximately one-half of the V beta 2+ T-cells were lost within the first month of C4 HAN implantation. Further reduction of V beta 2+ T-cells took place after another 3 months, at which time the level of V beta 2 was reduced to 1.2 +/- 0.1% of the total T-cell population. V beta 2 deletion occurred in BALB/c mice which had been implanted with C4 HAN at either 3 weeks or 2 months of age. Loss of V beta 2+ T-cells was not reversed by removal of C4 HAN. C4 tumor also induced V beta 2+ T-cell deletion. These results demonstrate a novel V beta 2 deleting activity expressed by C4 mammary lesions and suggest that during mouse mammary tumorigenesis, a unique "superantigen" is expressed which can cause profound systemic changes in the T-cell repertoire.