Rats received either 0 or 30 preexposures to a tone which was later used as a conditioned stimulus (CS) in a two-way avoidance task. Tone preexposure resulted in retarded conditioning in normal animals and animals with dorsal raphe lesions. This latent inhibition effect, however, was not present in animals with medial raphe lesions. The failure of CS preexposure to retard conditioning in animals with medial raphe lesions was not due to differences in auditory sensitivity or shock reactivity. Biochemical analysis indicated that whereas medial raphe lesions significantly reduced serotonin in the septohippocampal complex, dorsal raphe lesions had no such effect. The results are discussed in terms of the differing roles of the mesolimbic and mesostriatal serotonergic systems in learning to ignore irrelevant stimuli.