Attempts to replace a natural conditioned stimulus (taste) by electrical stimulation and a natural unconditioned stimulus (gastrointestinal disorder) by intracranial application of harmaline in the conditioned taste aversion (CTA) paradigm are described. The taste is replaced either by electrical stimulation of taste receptors of the tongue or by intracranial self-stimulation of the lateral hypothalamus, both triggered by licking. Both stimuli lose their rewarding properties when paired with gastrointestinal distress whereas self-stimulation triggered by nose poking is not affected by the same procedure. The unconditioned stimulus was replaced successfully by intracerebral injection of harmaline hydrochloride. The effect of the injection of 3-6 micrograms harmaline into the region of the inferior olive is comparable to that of systemic injection of 10 mg/kg harmaline. Electrophysiological analysis of the effect of locally and systemically applied harmaline indicates that the drug probably elicits CTA by activation of bulbar structures including the lateral reticular nucleus and lateral vestibular nucleus.