The effects of isoflurane on segmental spinal cord potentials and heterosegmental slow positive potentials in response to fore- and hindpaw stimulation were studied in the rat. The heterosegmental slow positive potential and late (second) component of the slow positive wave (P2) of segmental spinal cord potential, thought to be primary afferent depolarization, an agent of presynaptic inhibition activated by a feedback loopviasupraspinal structures, were greatly suppressed by the anesthetic. In contrast the negative wave (N1) of segmental spinal cord potential, believed to be synchronized activity of dorsal horn neurons, was only minimally affected. No differential effects of isoflurane on spinal cord potentials activated by fore- and hindpaws were found. Thus, the inhibitory activities of the spinal cord, particularly those produced by a feedback loopviasupraspinal structures, are suggested to be highly vulnerable to isoflurane.