Sera were obtained prior to conception and during the first trimester of subsequent pregnancies from 22 women over 27 pregnancies; on 15 occasions these pregnancies ended in spontaneous abortion, whereas the remaining 12 achieved live normal babies. In only one pregnancy ending in abortion could antibodies directed to paternal B-lymphocytes determined by the EA rosette inhibition (EAI) assay be detected in the mother's serum, whereas five of the 12 successful pregnancies were associated with such detectable antibodies. Cytotoxic antibodies were also found in all but one of these EAI-positive pregnancies and no antibody activity was present in sera obtained from five primigravidae. These results indicated that normal, but not abnormal, pregnancies were often associated with blocking antibody formation, suggesting that such antibodies may protect the fetus from abortion. However, the failure to detect antibody activity in sera from first trimester primigravidae argues against a central role for blocking antibody, alone, in the maintenance of outbred pregnancy.