Pregnancy has been known for some time to be associated with depressed aspects of cell-mediated immunity (CMI) that permit fetal retention but that also may interfere with resistance to specific infectious and neoplastic agents. Clinical and laboratory findings of loss of resistance have been extensively documented. Gestation appears to be associated with depression of selective aspects of CMI. Levels of hormones and other serum factors that may modulate lymphocyte or macrophage synthesis, activation, and/or function shift considerably during pregnancy. The induction and maintenance of pregnancy-associated immune deficiency probably rely on a multifactorial mechanism. Further research is needed to identify agents that would prevent fetal rejection while permitting adequate defense against infection and malignancy; to identify strains particularly dangerous during gestation; and to develop vaccines against the nonshared antigens of such strains.