This work examines the correlation between serum levels of oestrogen, progesterone and dehydroepiandrosterone sulphate (DHEA-S) and the number of human peripheral blood cells actively secreting interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) in vivo. Simultaneous assessment of serum hormone levels and cytokine-secreting cell activity throughout the menstrual cycle showed that the number of peripheral blood mononuclear cells (PBMC) able to secrete IL-4 in response to stimulation correlated significantly (P < 0.0001) with oestrogen levels and fluctuated with the menstrual cycle in pre-menopausal women. The activity of IFN-gamma-secreting cells, on the other hand, varied as a function of serum DHEA-S levels in pre-menopausal women (P < 0.0001). Similarly, the number of cells secreting IFN-gamma in men correlated with serum DHEA-S levels (P < 0.001). In contrast, post-menopausal women had fewer cells actively secreting cytokines and the activity of these cells did not correlate with sex hormone levels. These results suggest that sex hormones may modulate cytokine production in vivo and contribute to gender-related differences in normal and pathological immune responses.