Low-level alloreactivity between mother and fetus may provide stimulation for fetal T helper type 1 (Th1) cell immune maturation. This study explored the effects of human leucocyte antigen (HLA) mismatch on materno–fetal interactions detected as cytokine responses and lymphoproliferation in mixed lymphocyte reactions, and whether this was altered in allergic women (n = 62) who have a Th2 propensity compared with non-allergic women (n = 65). HLA-DRβ1 mismatch was associated with significantly increased Th1 interferon (IFN)-γ, Th2 interleukin (IL)-13 and lymphoproliferative responses by both mothers and fetuses. Allergic women showed significantly lower IFN-γ Th1 production in response to HLA-DRβ1 mismatch. The infants of these women also showed significantly lower IL-10 and lower IFN-γ production relative to IL-13. Both HLA-DRβ1 mismatch and maternal allergy had significant independent effects on maternal IFN-γ Th1 responses. Maternal allergy modifies HLA-mediated alloreactivity between the mother and the fetus, reducing Th1 activation. This may affect the cytokine milieu at the materno–fetal interface and could be implicated in the attenuated Th1 responses observed commonly in infants of atopic mothers.