An enzyme linked immunosorbent assay (ELISA) was used to estimate the production of intracellular and extracellular interleukin-1 (IL-1) alpha and beta by peripheral blood monocytes from 26 patients with various connective tissue diseases (CTD), including 19 with systemic lupus erythematosus, four with progressive systemic sclerosis, two with mixed connective tissue disease, and one with Sjögren's syndrome. Monocytes obtained from patients with CTD with serum antibodies to nuclear ribonucleoprotein (nRNP) released significantly higher concentrations of extracellular IL-1 alpha and IL-1 beta, whereas intracellular IL-1 alpha and IL-1 beta production was similar to that by monocytes from patients with CTD without antibodies to nRNP. Furthermore, the concentrations of extracellular IL-1 alpha correlated significantly with those of extracellular IL-1 beta. There was no significant correlation between the concentrations of extracellular and intracellular IL-1 alpha, and those of extracellular and intracellular IL-1 beta, indicating that synthesis and secretion of IL-1 by human monocytes may be two distinct biological events. It seems that enhanced extracellular release of both IL-1 alpha and IL-1 beta contributes to the excessive anti-nRNP production in CTD.