The physiological role(s) of fetuin, a protein present in plasma and many tissues of developing animals at levels much higher than in the adult, is unknown. Here we show that fetuin can modify the responses of macrophages to lipopolysaccharide (LPS) stimulation. At concentrations of fetuin in the medium, corresponding to fetal levels of this protein in plasma, the production and secretion of interleukin 1β (IL-1β) and nitric oxide (NO) is almost abolished, tumour necrosis factor-alpha (TNF-α) reduced, while that of IL-6 is not affected. On the other hand, concentrations of fetuin corresponding to adult plasma levels (i.e, 40-60 mg/100 ml) were without much effect on macrophage synthesis and secretion of these cytokines.