Intracellular recording from lumbar motoneurons of the neonatal rat spinal cord in vitro was used to study how recently developed non-peptide antagonists such as SR-140333 and SR-48698, known to block distinct subtypes of tachykinin receptors peripherally, might affect synaptic transmission elicited by electrical stimulation of dorsal root fibres. SR-140333 (1 microM) preferentially antagonized responses mediated by an exogenously applied agonist acting on the NK1 receptor subclass, while SR-48968 (0.5 microM) preferentially reduced responses mediated by an exogenously applied agonist acting on the NK2 receptor subclass. SR-48968 did not affect fast or slow excitatory postsynaptic potentials (EPSPs) or 'wind-up' responses induced by repetitive, low-frequency stimulation (mimicking certain types of nociceptive input); binding studies using this radiolabelled ligand disclosed specific binding activity (21 fmol/mg protein) selectively displaced by an NK2 receptor agonist. SR-140333 reduced the late component of fast and slow EPSPs, and of wind-up. Pharmacological block of ionotropic glutamate receptors abolished all dorsal root-evoked EPSPs. In comparison to glutamate receptor blockers, SR-140333 was a weaker antagonist of slow synaptic responses, though it displayed preferential antagonism towards some components of the wind-up phenomenon. The present results provide evidence obtained with a novel NK1 antagonist that a neuropeptide (presumably substance P), although not directly released by primary afferents onto motoneurons, is a neurotransmitter (acting via NK1 receptors) in the pathway mediating slow synaptic responses of motoneurons, and is presumably involved in signalling nociceptive inputs from the periphery.