The relationship of the depressant effect of baclofen on spinal monosynaptic transmission and its effect on the excitability of primary afferents was examined in spinal unanesthetized cats. Baclofen (1.0 mg/kg, i.v.) produced a deep and long-lasting depression of spinal reflex responses with a concomitant decrease of terminal excitability. Primary afferent depolarization, as indicated by an increase of terminal excitability, evoked by conditioning of an antagonistic muscle nerve, was greatly reduced by this drug. Depression of monosynaptic transmission induced by baclofen was temporarily reversed by posttetanic potentiation. However, the same high frequency orthodromic stimulation further reduced excitability of terminals. It is therefore unlikely that block of terminal invasion is responsible for baclofen-induced depression of spinal monosynaptic transmission. These results are compatible with the suggestion that baclofen causes a reduction of transmitter release. In the spinal cord, this action is probably limited to the excitatory transmitter of primary afferents.