- Balb/c (H-2d) mice were transfused weekly with 0.1 ml of whole blood from C3H/HeJ (C3H) (H-2k) mice. One and two weeks after each transfusion, mice were bled and the sera were collected and pooled. Serum samples from transfused mice were absorbed with erythrocytes and spleen cells from C3H mice, and then heat-inactivated. The presence of antiidiotypic antibodies in these sera was investigated using the mixed lymphocyte culture (MLC) inhibition test, in which spleen cells from normal Balb/c mice were tested for proliferative responses to x-irradiated C3H stimulator cells in the presence of sera from transfused mice. Sera obtained from transfused mice caused significant inhibition of responses in MLC. This inhibition in MLC was specific for stimulator cells from the blood donor (C3H), and little or no inhibition was observed with stimulator cells from third-party SJL mice. In addition, the inhibitory effect in MLC was specific for responder cells from the recipient Balb/c mice and no inhibition was observed with responder cells from blood donor C3H mice. These results suggest that blood transfusions induce antiidiotypic antibodies that can block the T cell antigen-specific receptors and cause inhibition of responses of the recipient mice to blood donor alloantigens in MLC. Thus in this strain combination, disparate for the entire H-2 region, antiidiotypic antibodies developed after 1 blood transfusion. These findings are in contrast to our earlier published results in which antiidiotypic antibodies developed after 3 transfusions in recipient-blood donor combination incompatible for the K and I regions. These data suggest that the development of antiidiotypic antibodies may be related to the level of histoincompatibility at the H-2 complex between recipient and the blood donor.