A review of the literature on interferons was conducted and possible roles in neuropsychiatric disorders with affective disturbances are assessed. Interferons and interferon receptors are present in the limbic system where they appear to exert physiological effects pertinent to affect, most potently when levels rise during CNS infections. Interferons interact closely with cytokines and nitric oxide, signaling molecules implicated in depression. Results from knock-out mice suggest a role for interferon-gamma in moderating fear and anxiety, while other lines of evidence point to a role in arousal and circadian rhythms. The interferon-alpha receptor deploys an arginine methyltransferase affecting RNA editing and splicing, which seem to be disrupted in schizophrenia and bipolar disorder. S-Adenosylmethionine (SAMe), an effective antidepressant, may owe its effects in the latter disorders in part to variations in the strength of interferon-alpha signaling impacting RNA processing. Antiviral effects of interferons are of interest in lieu of viral theories of affective disorders. Finally, the relative levels of interferons gamma and alpha might play important roles in neural, and glial, development, as well as the dialog between the CNS and the immune system. (C) 2001 Harcourt Publishers Ltd.