Soluble cytokine receptors (R) may regulate the activities of the cytokines present. We have studied the occurrence of soluble receptors for the cytokines tumor necrosis factor (TNF), interleukin-2 (IL-2) and interleukin-6 (IL-6) in normal pregnant women. Levels of TNFR and IL-2R were higher in retroplacental serum (RPS) than in the corresponding peripheral serum (PS) samples. TNFR, but neither IL-2R nor IL-6R, concentrations in PS from pregnant women were elevated compared to that in nonpregnant women. RPS inhibited TNF-mediated cytotoxicity, with the inhibitory effect being reduced after the removal of 55 kD TNFR from RPS. Our data reveal that soluble cytokine receptors are present in RPS and may contribute to the adjustment of intrauterine cytokine activities during pregnancy.