Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Several investigations have suggested that one of the mechanisms through which estrogen prevents bone loss was a modulation on secretion or release of various cytokines that are known to influence bone remodeling, even if some recent data have challenged this hypothesis. However, in established osteoporosis, the possibility that enhanced cytokines activity may account for the progression of this disease remains unclear and controversial. We sought here to determine whether production of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct stimulation in whole blood, was different in healthy (n = 30) or osteoporotic postmenopausal women (n = 24) and whether lumbar bone density (1-BMD) correlated with the values of cytokine production observed in these conditions. A significant difference was observed between the osteoporotic and control subjects for IL-1 beta (p < 0.0001), IL-6 (p < 0.001) and TNF-alpha (p = 0.027) productions, the values being higher in the osteoporotic women. No significant differences between the groups were observed for IFN-gamma (p = 0.51), GM-CSF (p = 0.70) or LIF (p = 0.97). In the whole population, statistically significant negative correlations were observed between lumbar BMD and IL-1 beta (r = -0.46) (p < 0.0005), IL-6 (r = -0.50) (p < 0.0001) and TNF-alpha (r = -0.39) (p < 0.005) production while no such correlations were observed for IFN-gamma, GM-CSF or LIF. In conclusion, the study of cytokine production by immune cells cultured in autologous whole blood suggests that in women more than 10 years past the menopause and presenting a decrease in lumbar bone density corresponding to the new WHO definition of "osteoporosis', production of IL-1 beta, IL-6 and TNF-alpha is still increased compared to controls matched for age and ovarian function, while no differences are reported for IFN-gamma, GM-CSF or LIF production.