Subdiaphragmatic vagally evoked unitary responses were recorded in the medial subnucleus of the nucleus tractus solitarius in an in vitro neonatal rat brain stem-gastric preparation. Substance P was applied to the gastric compartment and/or the brain stem compartment of the bath chamber to evaluate the peripheral gastric and central brain stem effects of the peptide on the nucleus tractus solitarius unitary activity. After substance P application to the gastric or brain stem compartment, a concentration-related change in the nucleus tractus solitarius unitary activity was observed. The gastric effects of substance P, at a concentration of 30 nM (minimum concentration for maximum effect), produced a 31 +/- 6.5% (mean +/- SD) increase in neuronal discharge frequency compared to the control recording. Both the proximal and the distal stomach were important in the gastric effect of the peptide on subdiaphragmatic vagally evoked nucleus tractus solitarius unitary responses. The brain stem effects of substance P. at a concentration of 10 nM (minimum concentration for maximum effect), induced a 52 +/- 11.3% increase in discharge frequency. Application of the peptide into both the gastric and brain stem compartments resulted in a subadditive response of 73 +/- 5.9%. This suggest that, peripherally and centrally, there are two different mechanisms of substance P activation. Our results suggest that substance P may play a role in regulating the ingestive process in neonates.