Secretion of soluble cytokine receptors has been suggested as a mechanism of regulating cytokine activity in vivo. In this study, the presence of soluble receptors for tumor necrosis factor-alpha (TNF-alpha) in serum samples from pregnant women and newborn babies was examined by using TNF-alpha receptor-specific immunoassays. Serum from pregnant women contained the 55-kD TNF-alpha receptor p55 [6.4 micrograms/L, interquartile range, i.e. the difference between the 25th and 75th percentile, (IQR) 7.2 micrograms/L], whereas p55 was not detected in control sera from nonpregnant, fertile women. The levels of p55 were also elevated in serum from newborns (3.2 micrograms/L, IQR 0.7 micrograms/L). Furthermore, first-voided urine from newborns contained high levels of p55 (44.6 micrograms/L, IQR 96.6 micrograms/L). The concentration of p55 in the neonatal period was significantly higher than that of children later in childhood (p < 0.05). The concentration of p55 was 7.3 micrograms/L, IQR 13.8 micrograms/L, in urine samples from a group of preschool children (1 mo < age < 5 y) and 6.9 micrograms/L, IQR 2.9 micrograms/L, in urine samples from children in a higher age group (5 y < age < 10 y). The concentration of the 75-kD TNF-alpha receptor in urine did not differ significantly between the different age groups studied. The elevated p55 serum levels of pregnant women and neonates are suggestive of a pregnancy-associated release of soluble receptors. The high concentration of p55 in neonatal urine may reflect a postpartum elimination of soluble receptors shed during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)