Interleukin-1 (IL-1) is a major mediator in infections and inflammation. Interleukin-1 receptor antagonist (IL-1ra) opposes the actions of IL-1. IL-1ra is present in exceptionally high concentrations in third trimester amniotic fluid. We studied IL-1ra in amniotic fluid, fetal serum and newborn urine. The concentrations of IL-1ra in amniotic fluid at mid-trimester and at 25-41 gestational weeks were 6.6 ± 0.5ng/ml (n = 30) and 100 ± 4ng/ml (n = 202), respectively. At mid-trimester, amniotic fluid IL-1ra was not dependent on fetal gender, whereas during the third trimester IL-1ra was higher in female- than in male-bearing gestations. Urine of normal term newborns during the first day of life contained a very high concentration of IL-1ra (125 ± 16ng/ml, n= 50). Urinary concentration in female newborns was significantly higher than that in male newborns (202 ± 19ng/ml, n = 25 versus 49 ± 14ng/ml, n = 25). IL-1ra concentration in fetal serum at 22-36 gestational weeks was 0.50 ± 0.07ng/ml (n= 31) and at term 1.5 ± 0.3ng/ml (n= 17). Serum concentrations were not gender-dependent. The gender differences in IL-1ra concentrations may in part explain the lower susceptibility of female fetuses to infection.