Taste aversion conditioning is characterized by its prompt acquisition despite the introduction of long delays between CS (taste) and UCS (toxic drug). Although the dramatic changes in behavioral response to a taste after this conditioning are well documented, relatively little is known about the changes in neural activity that accompany this learning. c-Fos immunohistochemical staining was employed to define brain regions activated during the expression of a conditioned taste aversion (CTA). The present studies examined c-Fos immunoreactivity in the brains of rats after i.p. injection of LiCl or NaCl or after intraoral infusion of a saccharin CS. LiCl administration, a common unconditioned stimulus (UCS) in CTA experiments, was found to induce c-Fos protein in a number of brainstem regions, including the nucleus of the solitary tract (NTS), medial and lateral pontine parabrachial nucleus (PBN), and hypoglossal nucleus. Conditioned animals received a single pairing of the CS saccharin with the UCS LiCl, while controls were exposed to the CS saccharin but received non-contingent LiCl 24 h after saccharin exposure. Following saccharin re-exposure, conditioned animals showed patterns of neuronal activation to a taste which were similar to those activated by the UCS drug. Specifically, the pattern of c-Fos expression in conditioned animals was confined to the same region of the NTS which showed the most activation following the UCS LiCl. This pattern of activation was not evident in controls re-exposed to saccharin.(ABSTRACT TRUNCATED AT 250 WORDS)