Secretion of soluble cytokine receptors has been suggested as a mechanism for regulation of cytokine activity in vivo. The present investigation was performed to study whether secretion of soluble TNF (tumor necrosis factor) receptors (TNFRs) might be associated with pregnancy. There are two known molecular species of the TNFR, the 55-kDa TNFR and the 75-kDa TNFR. The 75-kDa, as well as the 55-kDa TNFR, was detected in urine from pregnant women, whereas only the 75-kDa TNFR was detected in urine from the non-pregnant group. The concentration of TNFRs in urine increased towards term and was reduced in association with spontaneous delivery. The soluble forms of both TNFRs were also detected in amniotic fluid. Collectively, the data suggest that secretion of soluble TNFRs during pregnancy might be a defence mechanism for the protection of the fetus against TNF action.