This study investigated immunoregulatory differences as a result of anatomical changes in the fetomaternal interface. Thirty-one female subjects were recruited from a military tertiary-care facility. Ten subjects were non-pregnant while 21 were pregnant (nine normal and 12 ectopic gestations). Immune tests included one-way mixed lymphocyte cultures with and without maternal plasma, phytohemagglutinin stimulation and lymphocyte phenotypes. Basic statistics and a one-way ANOVA using Tuckey's HSD model were employed. Autologous plasma significantly enhanced the allogeneic responses of first-trimester pregnant females with normal gestations to spouses as well as to control male lymphocytes. This enhancement was not observed in either ectopically-pregnant or non-pregnant subjects. Mitogen stimulation and lymphocyte populations were similar in all three groups. The first trimester of normal pregnancy is characterized by the presence of soluble intrauterine pregnancy-specific lymphocyte-enhancing factors. Ectopic gestation lacks this phenomenon.