Two hundred and three sera obtained from multiparous women were screened to determine the frequency of the appearance of antibodies reactive with PHA-activated T lymphocytes, but not with resting B or T cells from the same donor. The panel of cells on which the sera were tested consisted of lymphocytes from 38 unrelated donors known to be homozygous at the HLA-D locus. Forty-two sera were shown to react uniquely with PHA-activated T cells. The reactivities of these sera could not be explained in terms of the defined HLA-A,-B,-C, or DR antigen specificities on the panel cells, nor on the basis of known cross-reactivities among these antigens. Most of the antisera showed strong cytotoxicity with the activated T cells. Such sera may define antigens presented to the maternal immune system during differentiation and development, which are not expressed on adult T cells unless they are activated.