This study characterizes the inputs from the lateral columns of the spinal cord to reticulospinal neurons in the lampreys, using the in vitro isolated brainstem and spinal cord preparation. Synaptic responses to the electrical stimulation of the lateral columns were recorded in reticulospinal neurons of the posterior and middle rhombencephalic reticular nuclei. The responses consisted of a mixture of excitation and inhibition. They were markedly potentiated when using trains of two to five pulses, suggesting that the larger part of these synaptic responses was mediated via an oligosynaptic pathway. An early component, however, persisted when using twin pulses at 10-20 Hz on the ipsilateral side, suggesting the presence of an early mono- or disynaptic component. When increasing the stimulation strength, an early fast rising excitatory component appeared. It most likely resulted from an antidromic activation of vestibulospinal axons in the lateral tracts, which make en passant synaptic contacts with reticulospinal neurons. Responses were practically abolished by adding CNQX and AP5 to the Ringer's solution. The late component of excitatory responses was decreased by AP5, suggesting that NMDA receptors were activated. The NMDA receptor-mediated component was larger when using trains of stimuli or in Mg2+-free Ringer's. The application of NMDA depolarized reticulospinal neurons. The glycinergic inhibitory component was markedly increased in Mg2+-free Ringer's. Moreover, GABAB-receptor activation with (-)-baclofen abolished both excitatory and inhibitory responses. Taken together, the present results indicate that ascending lateral column axons generate large excitatory and inhibitory synaptic potentials in reticulospinal neurons. The possible role of these inputs in modulating the activity of reticulospinal neurons during locomotion is discussed.