Cytokine expression at the maternal-fetal interface is well documented. Some authors have postulated the existence of a bidirectional cytokine signaling mechanism that is critical to the maintenance of normal pregnancy. The role of the fetus (versus fetally derived placental tissues) in this process is unknown. Using reverse transcription polymerase chain reaction techniques, we studied paired maternal and fetal samples from 16 pregnancies (including two twin pregnancies) for the presence of tumor necrosis factor-alpha and IL-1 beta mRNA. We demonstrate that mRNA for both of these cytokines can be detected in both maternal and fetal blood as early as the 21st wk of gestation. These results support a potential role for the fetus in the bidirectional cytokine signaling of pregnancy.