Neurons located in the medial septum-nucleus of the diagonal band of Broca (vertical limb) and antidromically activated by electrical stimulation of the fimbria were recorded in urethane anesthetized rats. Forty-three percent of these septohippocampal neurons (SHNs) were excited by the iontophoretic application of thyrotropin-releasing hormone (TRH). Rhythmically bursting SHNs were more often excited (63%) by TRH than the non-bursting SHNs (35%). The majority of the TRH-sensitive SHNs could also be excited by cholinergic agonists. TRH-induced excitations were not abolished by the simultaneous application of atropine. Potentiation by TRH of acetylcholine, carbachol or glutamate-induced excitations of SHNs were rarely observed. Cyclo (His-Pro) and (3-Me-His2)-TRH were observed to have similar, although less dramatic, effects. These results demonstrate that the SHNs, which are the neurons of origin of the septohippocampal pathway, are readily excited by TRH.