We determined the interferon (IFN) serum levels and in vitro activated IFN production in eight patients with relapsing/ remitting multiple sclerosis (MS), using a whole-blood test system and the mitogen concanavalin A and the viral antigen Newcastle disease virus for induction of the IFN production. During the overall study period of 12 months we observed, in relation to clinical disease progression, a biphasic increase in the individual IFN alpha and IFN gamma production. While mitogen-induced IFN gamma synthesis showed a significant augmentation prior to the onset of a new relapse (P < 0.05), virus-induced IFN alpha production showed a temporal delayed increase which was related to clinical remission (P < 0.01). The observed fluctuations in the individual production of both IFN subtypes were not reflected in the sera of the patients. Although the reason for the temporal different imbalance in the production of both IFN subtypes remains unknown, the observed association between increased IFN alpha production and clinical remission emphasizes a possible role for type 1 IFNs in the resolution of the MS relapse.