State-dependent learning is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same sensory context and physiological state as during the encoding phase. In spite of extensive behavioural and pharmacological characterization, no cellular counterpart of this phenomenon has been reported. Here we describe a neuronal analogue of state-dependent learning in which cortical neurons show an acetylcholine-dependent expression of an acetylcholine-induced functional plasticity. This was demonstrated on neurons of rat somatosensory 'barrel' cortex, whose tunings to the temporal frequency of whisker deflections were modified by cellular conditioning. Pairing whisker stimulation with acetylcholine applied iontophoretically yielded selective lasting modification of responses, the expression of which depended on the presence of exogenous acetylcholine. Administration of acetylcholine during testing revealed frequency-specific changes in response that were not expressed when tested without acetylcholine or when the muscarinic antagonist, atropine, was applied concomitantly. Our results suggest that both acquisition and recall can be controlled by the cortical release of acetylcholine.