The actions of substance P and thyrotropin-releasing hormone (TRH) on neonatal rat spinal motoneurones in vitro were compared using intracellular current and voltage clamp techniques. Like TRH, substance P evoked a slowly-developing, persistent depolarisation plus an increase in input resistance under current clamp conditions. Under voltage clamp conditions, substance P elicited an inward current (mainly due to a conductance block) which peaked near -40 mV and reversed polarity close to the estimated EK. A distinct conductance increase (with a reversal potential near zero) also appeared to contribute to this response. The response to substance P at resting potential was suppressed by 1.5 mM Ba2+, but not by 20 mM tetraethylammonium, 2 mM 4-aminopyridine, 2 mM Cs+ and 0.2 mM Cd2+. In addition, co-application of TRH and substance P mutually occluded each other. Thus, it is suggested that substance P and TRH share a common effector mechanism, which primarily involves the suppression of IK(T), a persistent K+ current recently discovered in these neurones.