Serum concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)-1beta, and their circulating inhibitors soluble TNF receptor type I (sTNFRI), type II (sTNFRII), IL-1 receptor antagonist (IL-1ra), and soluble IL-1 receptor type II (sIL-1RII) were measured for 123 patients with tuberculosis (TB) in various stages of disease, in persons who had been in close contact with patients with contagious pulmonary TB, and in healthy controls. Levels of sTNFRI, sTNFRII, and IL-1ra, but not of sIL-1RII, were elevated in patients with active TB compared with contacts and controls and declined during treatment. The concentrations of these mediators did not differ between patients with pulmonary and extrapulmonary TB. The levels of sTNFRI and IL-1ra were higher in patients with fever and anorexia. Neither TNF nor IL-beta was detectable. We conclude that serum concentrations of sTNFRs I and II and IL-1ra may serve as markers of disease activity of TB. Sequential measurements of these cytokine inhibitors may be useful in the monitoring of antituberculous therapy.