The present investigation determined whether an immunomodulator agent modified the central nervous system activity as measured behaviorally and neurophysiologically. Two types of interferons (IFNs), alpha (alpha) and gamma (gamma), were applied locally (microiontophoretically) into various regions of the rat brain simultaneously with single neuron recording from the cerebral cortex, hippocampus, thalamus and hypothalamus. Of the various IFNs, only alpha-IFN altered single cell activity in all brain structures in a dose-dependent manner. Moreover, systemic administration of alpha-IFN altered the naloxone-induced abstinence syndrome in morphine-dependent rats. These observations suggest that immunomodulators such as alpha-IFN are capable of influencing directly central nervous system function as well as the immune system.