Uterine natural killer (uNK) cells belong to the large granular lymphocytes in the murine pregnant uterus and play essential roles in pregnancy success. We defined whether uNK cells can produce epidermal growth factor (EGF) important for implantation and embryo growth. The uNK cells were immunohistochemically positive for anti-EGF antibody especially during days 6 to 9 and at day 15 of pregnancy. Immunoreaction for EGF receptor was observed on the stromal cells in the metrial gland and trophoblasts in the placental labyrinth. EGF secretion (72.1 +/- 2.25 ng/10(40 cells) was noted in cultured uNK cells isolated from the metrial gland at day 15 of pregnancy. Treatment of anti-asialo-GM I antibody raised the level of EGF (129 +/- 21.5 ng/10(4) cells). These results suggest uNK cell can produce and release EGF for placental development.