Peripheral blood lymphocytes from patients with multiple sclerosis (MS) have been shown by numerous investigators to function abnormally in a variety of immunological tests in vitro. In this article, data concerning defective natural killer (NK) cell function and interferon production by MS patients' lymphocytes have been reviewed. Production of IFN-alpha and IFN-gamma by appropriately stimulated lymphocytes has been shown to be significantly reduced in many patients with acute remitting or chronic progressive disease. Furthermore, a significant proportion of these patients has been found to exhibit reduced levels of endogenous and augmented NK cell activity. A likely explanation for these phenomena is that altered traffic occurring as a consequence of disease has led to a relative loss of NK and IFN-producing cells from the peripheral circulation. Flow cytometric data obtained using monoclonal antibodies that selectively label these effector populations were presented. Possible explanations for the observed defects and their significance relative to our understanding of the etiopathogenesis of MS were discussed.