Two experiments evaluated the effects of depletion of forebrain norepinephrine (NE) or serotonin (5-HT) on two forms of internal inhibition. Experiment 1 examined the role of NE and 5-HT depletion on latent inhibition: rats with dorsal bundle or raphe lesions or vehicle control rats were trained to one of two pre-exposure conditions (single vs multiple stimuli) or to a non-pre-exposure control prior to conditioning. The results of this experiment showed that latent inhibition was attenuated under either condition of pre-exposure following depletion of 5-HT but that attenuation was present in NE depleted rats only when pre-exposed to multiple stimuli. Experiment 2 assessed the rate at which a conditioned inhibitor was established following NE or 5-HT depletion. The results of Experiment 2 indicated that the formation of a conditioned inhibitor was unimpaired following depletion of either NE or 5-HT. The results of Experiment 1 demonstrate that 5-HT and NE have different effects on associative processes: 5-HT apparently affects a habituation-like process, whereas NE is an important influence on more complex mechanisms involving the comparison of new with previously acquired information. The findings of Experiment 2 are consistent with behavioral investigations which show that conditioned inhibition affects output processes rather than the salience of stimuli.