The present study demonstrates sites of expression for Fos protein in the brainstem and lumbosacral spinal cord of rats subjected to mustard oil irritation of the colon. The protective effect of baclofen, a selective GABA(B) receptor agonist, on the induced Fos protein increases was determined. Mustard oil injected into the lumen of the colon produces an acute site-specific inflammation. Immunocytochemical localization of Fos protein in neuronal nuclei was evident after 1 h, was greatest at 2 h and was still evident but declining at 8 h. In the spinal cord the majority of Fos labeled neurons were localized in the superficial laminae of lumbar (L6) cord with more found in the sacral (S1) cord. Some labeled neurons were also found in the deeper spinal laminae, intermediolateral nucleus and around lamina X. Brainstem sites expressing Fos included the nucleus of the solitary tract in the medulla, parabrachial, locus coeruleus, pontine and caudal dorsal raphe nuclei and periaqueductal gray. Weak Fos protein labeling existed in a few cells in vehicle control animals. Systemic administration of the GABA(B) receptor agonist, baclofen (10 mg/kg, i.p.), significantly reduced Fos expression in the spinal cord after mustard oil treatment but significantly increased the relative number of nuclei labeled in the nucleus of the solitary tract. Baclofen also significantly decreases dorsal horn CGRP immunoreactivity relative to the increased levels seen after inflammation of the colon. The SP content increases observed after inflammation of the colon were not altered by baclofen. These data suggest that: (1) neurons in regions important for nociceptive transmission, descending inhibitory control and autonomic control are activated by noxious stimulation of the colon, and (2) baclofen specifically reduces Fos expression in the superficial dorsal horn of the spinal cord induced by nociceptive afferent input.