The present study investigates the effect of different endocrine manipulations on the gamma-aminobutyric acid (GABA)-ergic system in the rat fallopian tube. Either hypophysectomy or ovariectomy induced a significant decrease of glutamic acid decarboxylase (GAD) activity and of GABA levels in in situ tubes. This effect was completely reversed by either gonadotropins or combined estrogen-progesterone administration, respectively. Estrogen or progesterone alone proved less effective than the administration of both steroids in counteracting the effect of ovariectomy on GAD activity. The in vitro incubation of ovariectomized rat fallopian tubes with estrogen-progesterone for 1 h failed to counteract the reduction of the GAd activity induced by surgical manipulation. The in vivo effect of estrogen-progesterone administration on the GABA-ergic system seems to be specific since steroid treatment induced the synthesis of an enzyme which was immunologically identical to the GAD present in the fallopian tube and brain of normal diestrous rat. Autotransplantation of the fallopian tube under the skin brought about a decrease of GAD activity similar to that obtained after ovariectomy. In this situation, however, estrogen-progesterone administration did not counteract the decrease of GAD activity induced by fallopian tube deafferentation. The present results demonstrate that an interaction between the GABA-ergic system and the hypothalamo-pituitary-gonadal axis seems to be operative at the level of the rat fallopian tube. However, the physiological meaning of this interrelationship between the endocrine and the peripheral nervous systems remains to be clarified.