Background: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood ( CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. Methods: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ ovalbumin ( OVA) or house dust mite (HDM)] and mitogens [ concanavalin A ( ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy ( n = 17) with responses of neonates whose mothers never smoked ( n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [ interleukin (IL)-13, IL-6, interferon (IFN) gamma and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNgamma). Results: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM ( P = 0.01) and OVA ( P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNgamma mRNA responses to PHA ( P = 0.015) and ConA ( P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNgamma protein responses to allergens or mitogens. Conclusions: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.