Serum levels of alpha (alpha) and gamma (gamma)-interferons (IFN) were measured in 30 patients with untreated systemic lupus erythematosus (SLE) with a solid-phase, sandwich immunoradiometric assay using specific monoclonal antibodies. The serum levels of alpha-IFN were higher in patients with SLE than in normal subjects, and correlated with the clinical activity index (rs = 0.60, P less than 0.01), but not with renal histological activity. The serum level of alpha-IFN correlated with the serum level of immune complexes (r = 0.46, P less than 0.01) and the number of peripheral lymphocytes inversely (r = -0.49, P less than 0.01). Serum gamma-IFN levels were also higher in patients with SLE than in control subjects but no correlations were found between it and either clinical activity, renal histological activity or various laboratory parameters. Serum levels of both alpha-IFN and gamma-IFN were higher in SLE patients with erythema than in those without. These results suggested that serum levels of alpha-IFN were more closely related to clinical activity of SLE than were those of gamma-IFN, and that peripheral lymphocytes were probably not the source of the elevated serum IFN-alpha concentration.