An autoreactive T lymphocyte clone, designated as F1C4 was established from an autoimmune mouse strain (NZB/NZW)F1. This clone proliferated in the presence of mitomycin C-treated splenic adherent cells (MMC-SAC) from syngeneic mice. This response was dependent on the numbers of MMC-SAC. The specificity of F1C4 for I-A was determined by an inhibition test carried out with monoclonal anti-Ia sera. Furthermore, the F1C4 cells did not exhibit alloreactivity in a proliferation assay and did not react to foreign antigens such as fetal calf serum (FCA) used in the culture medium. When F1C4 cells were cultured with autologous non-T cells in the absence of antigen, they strongly enhanced IgM class anti-ssDNA production from non-T cells of both young and old B/W F1 mice at appropriate cell numbers in vitro. Furthermore, the production of IgG class anti-ssDNA from non-T cells of old B/W F1 mice was also enhanced. The adoptive transfer of F1C4 cells enhanced the levels of both IgM and IgG anti-ssDNA antibodies in the serum of aged B/W F1 mice. Moreover, the serum levels of anti-ssDNA of IgG2a and IgG2b subclasses were readily enhanced by the transfer of F1C4 in vivo.