Whole-cell patch recordings of neurons in the rostral (gustatory) nucleus tractus solitarius (rNTS) were performed in a brain slice preparation from rat medulla. Neural responses to brief applications (10-45 s) of substance P (SP), via a constant superfusion apparatus, were recorded. SP transiently depolarized 80 of 117 (68%) rNTS neurons in a dose-dependent manner. Sub-micromolar concentrations of SP had potent excitatory effects, and the half maximal response occurred at 0.6 microM. The depolarizing effect of SP was accompanied by an increase in input resistance in 81% of the responsive neurons. The excitatory effects of SP persisted in low Ca2+ (0.2 mM) and high Mg2+ (12 mM) saline as well as in the presence of 2 microM TTX (n = 5 for each), suggesting direct postsynaptic action on the recorded neurons. SP also hyperpolarized 4 neurons (4%) and had no effect on 33 neurons (28%). Each of the 4 neurons which were hyperpolarized by SP showed a decrease in input resistance. A more detailed assessment of the types of neurons in the rNTS which respond to SP was also conducted. Neurons were separated into 4 electrophysiological groups on the basis of their repetitive firing pattern induced by a hyperpolarizing and depolarizing current injection paradigm. Neurons belonging to each of the 4 electrophysiological groups responded to SP. Eighteen neurons, which were filled with 1% biocytin during recording, were categorized as ovoid, multipolar or fusiform based on their morphological characteristics. SP excited all 3 morphological types of neurons in similar proportion. These results suggest that SP is an excitatory neurotransmitter in the rNTS. The effects of SP are not restricted to a particular neuron type defined either biophysically or morphologically. The implications of these results on the possible role of SP in processing gustatory and somatosensory information within the rNTS are discussed.