Steroid hormones including sex hormones are known to influence cytokine production by cells in vitro. We investigated whether there are differences in cytokine production in vivo and ex vivo during the menstrual cycle in five ovulating women compared with five pregnant women and nine males. Interleukin 6 (IL-6) in plasma changed periodically during 12 of 13 cycles in five women. The IL-6 levels were lowest in the luteal phase when progesterone levels were elevated and highest preovulatory when progesterone levels were low (P < 0.009). This phenomenon was unrelated to changes in haematocrit or albumin and independent of cortisone, growth hormone, luteinizing or follicle stimulating hormone and testosterone. In contrast to IL-6, the soluble IL-6 receptor did not vary significantly during the menstrual cycle. In comparison, nine males and five pregnant women had low plasma IL-6 levels comparable with women during the luteal phase. In addition, levels of IL-6, IL-10 and TNF were determined after whole blood stimulation with lipopolysaccharide ex vivo during a menstrual cycle. Neither the number of CD-14++ or CD14/CD16+ cells nor the amounts of IL-6, IL-10 and TNF after stimulation showed cyclic changes. We suggest that sex hormones, especially oestrogen and progesterone, may influence immune responses by decreasing basal IL-6 levels in vivo.