BACKGROUND Since dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suggested to have immunoregulatory effects, changes in the levels of these substances during and after pregnancy might affect the maternal immune system. We examined serum concentrations of DHEA and DHEAS, and cytokine production during pregnancy and after delivery. METHODS The subjects were 73 normal pregnant, 76 normal postpartum and 30 normal non-pregnant women. Whole-blood was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin and the levels of cytokines in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). DHEA and DHEAS were measured using ELISA and gas chromatography-mass spectrometry (GC-MS), respectively. RESULTS The serum DHEA levels increased in the first and in the second trimesters and decreased after delivery until 11 months postpartum. DHEAS levels were decreased in the second and in the third trimesters and returned to non-pregnant levels after pregnancy. All measured cytokines (IFN-gamma, IL-2, IL-4 and IL-10) were decreased during pregnancy and subsequently increased postpartum. We found significant negative correlations between DHEA and cytokine levels. CONCLUSIONS Increase of serum DHEA in the first and the second trimesters may suppress immune reaction during pregnancy, while a decrease of DHEA after delivery may induce postpartum enhancement of the maternal immune system. DHEA may be involved in modifying the maternal immune responses during and after pregnancy.