Most congenital transmissions of Trypanosoma cruzi are not detected. As the levels of mediators regulating the immune response might be different in the absence or in the presence of transmission, we explored the levels of tumor necrosis factor (TNF) and soluble TNF receptors TNF-R1 and -R2 in T. cruzi-infected pregnant women and the neonates. We previously found that the circulating levels of TNF were higher in non-transmitting than in transmitting pregnant women. This observation has now been extended to the spontaneous release of TNF by peripheral blood leukocytes (PBLs) that was also higher in non-transmitting than in transmitting pregnant women. As their mothers, non-infected neonates had higher circulating levels of TNF than congenitally infected children. The circulating levels of sTNF-R1 increased in non-transmitting and transmitting mothers and in infected and non-infected neonates. The circulating levels of sTNF-R2 were approximately 60% higher in infected than in non-infected neonates (1,635 +/- 101 and 1,027 +/- 100 pg/mL, respectively) and remained higher at 1 year of age. This important increase, only observed in infected neonates, could be useful to orientate to the presence of vertical transmission of T. cruzi infection.