To investigate the distribution of Fos-like immunoreactivity (FLI) in the central nervous system of urethane anesthetized rats after activation of a somatosympathetic reflex pathway, the cut central end of the right femoral nerve of 17 male Wistar rats was stimulated electrically for 1 h at parameters such that increases in heart rate and arterial pressure were elicited. Sections of brain and spinal cord were incubated in anti-Fos antibody and the presence of FLI was detected using the ABC immunoperoxidase method. In the spinal cord FLI was present in the ipsilateral lumbar spinal cord (laminae 1 and 2, 4-6 and 10) and contralateral intermediolateral nucleus in the thoracic spinal cord. In the hindbrain, FLI was present in the contralateral rostral ventrolateral medulla and bilaterally in the cochlear nucleus, external cuneate nucleus, locus coeruleus and lateral parabrachial nucleus. In the midbrain, label appeared in the Edinger-Westphal nucleus and peripeduncular nucleus on both sides. In the forebrain, FLI appeared bilaterally in the central nucleus of the amygdala, para- and periventricular hypothalamus, supraoptic nucleus, paraventricular thalamus, reuniens nucleus, subfornical organ and bed nucleus of the stria terminalis. These results define the central nervous system pathways of somatosympathetic reflexes and demonstrate that areas in the forebrain not previously known to be activated by somatosympathetic reflexes, but previously implicated in mediating the defense reaction, are activated by these reflexes.