Interferon production after stimulation of lymphocytes with purified protein derivative, pokeweed mitogen, and phytohemagglutinin was studied in 39 patients with stable multiple sclerosis (MS) and 39 age- and sex-matched controls. Stable MS patients produced less interferon, and the number of subjects producing undetectable amounts of interferon was higher in the MS group (11/39) than in the control group (2/39). A tendency toward an association between low interferon production and HLA-Dw2 antigen was found in MS patients. There was no clear-cut correlation between interferon production and the duration of disease or disability of the patients. Although there was no systematic correlation of age with interferon production, patients older than 55 years tended to be very poor interferon producers.