1 The effects of baclofen have been examined on responses of neurones in the spinal cord of the anaesthetized cat to stimulation of appropriate synaptic pathways, acetylcholine and a range of amino acid excitants. Baclofen and excitant substances were administered by standard microiontophoretic techniques. 2 Small ejecting currents of baclofen (less than 10 nA) depressed non-cholinergic, excitatory, synaptic responses evoked by stimulation of dorsal roots or muscle or cutaneous afferents. Excitatory monosynaptic responses were particularly sensitive to the depressant action of baclofen. 3 Spontaneous firing in neurones was sometimes reduced in parallel with synaptic excitatory responses, but synaptically evoked inhibition was unaffected and ventral root evoked excitation of Renshaw cells was either unaffected or enhanced by baclofen. 4 Ejecting currents of baclofen which markedly depressed excitatory synaptic responses either had no effect or minimal depressant effects on responses induced by iontophoretically administered acetylcholine and excitant amino acids. However, relatively large currents of baclofen (e.g. 20 to 40 nA) reduced excitatory responses to exogenously administered excitants. 5 It is suggested that baclofen depresses (a) synaptic response by an action on excitatory nerve terminals and (b) responses to exogenous excitants via a postsynaptic action. 6 Comparison of baclofen with a number of other substances indicates that the depression of noncholinergic, excitatory, synaptic responses is unlikely to involve an interaction of this agent with receptors for monoamines, 5-hydroxytryptamine or the inhibitory amino acids, gamma-aminobutyric acid and glycine.