Interleukin-1 is a family of polypeptides with a wide spectrum of immunoinflammatory activities pertinent to Crohn's disease, including T-cell activation. Using specific enzyme-linked immunosorbent assays, only sera from two of 19 patients (11%) with active Crohn's disease contained interleukin-1 alpha and interleukin-1 beta activity. Using the thymocyte proliferation assay, sera from the same patients contained significantly increased inhibitory activity against interleukin-1 alpha (P = 0.025) and interleukin-1 beta-induced cell activation (P = 0.00005) as compared with controls. Changes in both interleukin-1 alpha (P = 0.020) and interleukin-1 beta (P = 0.012) inhibitor concentrations correlated significantly with changes in clinical disease activity. None of the patient sera contained IgG or IgM autoantibodies to IL-1 alpha, nor did they exert significant inhibitory activity against interleukin 1 beta in the fibroblast prostaglandin E2-induction assay. Taken together, these data provide evidence for the presence of one or several regulators of interleukin-1-induced T-cell activation in sera from patients with active Crohn's disease.