Idiotypic T-cell receptors for antigen have been identified in previous studies by use of anti-clonotypic monoclonal antibodies. To determine whether anti-receptor autoantibodies play a role in immune regulation, we have used normal pregnancy as a model. T-cell clones were generated from the peripheral blood of a primiparous woman by priming her lymphocytes to stimulating cells from her husband. As a control, T cells primed to lymphocytes from HLA different controls were used. Purified IgG was prepared from this woman's serum and tested for its reactivity with cell surface antigens expressed by autologous T-cell clones. We have identified one anti-HLA-DR reactive clone specific for the immunizing HLA haplotype of the child that reacted with autologous F(ab')2 in immunofluorescence studies. When tested in functional studies, the F(ab')2 blocked the capacity of the clone to lyse specific target cells, while triggering clonal proliferation in the absence of stimulating cells. The determinant(s) recognized by autoantibodies in the F(ab')2 preparation comodulate with the T3 antigen present on the surface of the cells. These data suggest that sera obtained during pregnancy contain autoantibodies which behave similarly to heterologous anti-clonotypic antibodies. Such anti-T-cell receptor antibodies may play a role in maternal tolerance to the fetus.