We examined the effects of NGF on the TGC (trophoblastic giant cell) transformation of the ectoplacental cone (EPC) cells derived from the mouse pregnant uteri on day 7.5 p.c. The addition of NGF strongly accelerated the rate of the TGC transformation of EPC cells in a dose-dependent manner. The promoting action of NGF was abolished by the addition of anti-NGF MAb. Histochemical staining with succinyl wheat germ agglutinin (s-WGA), an in situ marker for the TGCs on day 10.5 p.c., revealed that NGF induced the expression of s-WGA-binding glycoproteins in TGCs in vitro. RNA analysis revealed that NGF mRNA was expressed in the pregnant uterus on day 7.5 p.c., mainly in the decidua, but it could not be detected in the EPC. p75NGFR mRNA was expressed in the EPCs, whereas TrkA mRNA was not detected in the placental tissues throughout day 7.5 to 10.5 p.c. We therefore conclude that maternally derived NGF may play a role in mouse placentation by promoting the giant-cell transformation of trophoblast cells through p75NGFR.