The isolated, hemisected spinal cord of the frog has been used to examine the action of peptides on frogs motoneurons. Both sucrose gap recording from the ventral roots and intracellular microelectrode recording were used. Substance P (SP), thyrotropin-releasing hormone (TRH), neurotensin and bombesin all had a depolarizing action. The responses to neurotensin and bombesin were blocked by tetrodotoxin suggesting that their action was indirectly mediated through interneurons. SP and TRH had a direct depolarizing action on motoneurons. SP was slightly more active and TRH slightly less active than glutamate. The responses to both peptides had a slower time course than the responses to glutamate. The maximum depolarizations produced by the peptides rarely surpassed the firing threshold of the motoneurons. However, their excitability was increased, since subthreshold synaptic potentials and responses to current injection surpassed threshold during the peptide responses. In approximately half of the cells tested, a small decrease in membrane resistance could be detected during the peptide responses. These results suggest that if SP and TRH were released from synapses impinging on frog motoneurons they would exert a background excitatory action.