In the leukocyte adherence inhibition (LAI) assay, about 34% of adherent T-cells from patients with breast cancer exhibit nonadherence to glass when incubated with extracts of autologous cancer but not with HLA-A, -B, and -C mismatched extracts of breast cancer. To determine whether the recognition by T-cells of tumor antigen was major histocompatibility complex restricted, major histocompatibility complex antigens in the cancer extracts or on the T-cells were coated with monoclonal antibody (MAb) to nonpolymorphic determinants. Nonadherence of T-cells was antagonized by coating the target cancer extracts with MAb to a common framework determinant of Class I HLA-A, -B, and -C antigens or to the nonpolymorphic beta 2-microglobulin, which is noncovalently associated with Class I antigens. By contrast, a MAb to a monomorphic determinant on HLA-DR antigens did not change the positive T-cell response. Moreover, coating the T-cells with MAb to HLA-A, -B, and -C did not inhibit the positive T-cell response. The positive LAI response of buffy coat peripheral blood leukocytes from patients with breast cancer to extracts of allogeneic breast cancer was not affected by coating the cancer extracts with the same MAb, indicating that MAb inhibited T-cell LAI specifically and that the antibody-dependent LAI response of buffy coat peripheral blood leukocytes was not major histocompatibility complex restricted. The results indicate that HLA-A, -B, and -C antigens in extracts of autologous breast cancer restrict the LAI response to tumor antigens of T-cells from patients with breast cancer.