The effects of intracerebroventricular (i.c.v.) administration of substance P (SP) and gamma-aminobutyric acid (GABA) on responses evoked in the nucleus tractus solitarii (NTS) by electrical stimulation of the ipsilateral sinusal nerve were studied in alpha-chloralose-anesthetized rats. Both SP (0.01-10 micrograms) and GABA (100 micrograms) significantly depressed the presumably C-fiber mediated, late negative wave of the response. The effects were almost completely prevented by bicuculline (10 micrograms i.c.v.). It is concluded that i.c.v. administered SP induces dose-dependent depression of baro- and/or chemosensory transmission in the NTS, via a mechanism involving interactions with GABAergic neurons of the NTS.