The production of interleukin-1 (IL-1) by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and inactive phase, in chronic progressive MS patients, in other neurological diseases, and in healthy subjects. Production was determined by measuring the IL-1 concentration in cultures with MNC supernatants using enzyme-linked immunosorbent assay (ELISA). IL-1 in sera of MS patients and healthy subjects also was investigated. MNC IL-1 alpha production was significantly higher in MS patients (180.2 +/- 177.5 pg/ml) than in healthy subjects (66.2 +/- 66.0 pg/ml) (P less than 0.05). Relapsing MS patients in the active phase had significantly higher MNC IL-1 alpha concentrations (360.1 +/- 130.0 pg/ml) than normal subjects (P less than 0.001), but MNC IL-1 alpha production in patients with relapsing MS in the inactive phase (65.3 +/- 52.8 pg/ml) or chronic progressive MS (80.9 +/- 71.9 pg/ml) was not increased significantly. MNC IL-1 beta production in MS patients was not elevated significantly. IL-1 alpha and -1 beta were not detected in sera of MS patients. The correlation between increased IL-1 alpha production and the clinical course of MS suggests that activated MNC may play a role in the pathogenesis of MS.