In order to determine whether tuberculosis is associated with elevated levels of soluble interleukin-2 receptors (SIL-2R), patients with both pulmonary (n = 12) and extrapulmonary (n = 8) disease were studied. SIL-2R were measured in sera using an enzyme-linked immunosorbent assay (ELISA). Prior to treatment, all 20 patients had levels of SIL-2R significantly greater than those of the 14 control subjects. Longitudinal study of patients with pulmonary disease revealed that levels of SIL-2R remained elevated in 11 of 12 patients after 2 months, and in four of six patients after 3 months of treatment. These findings suggest that tuberculosis is characterized by prolonged activation of the immune system despite optimal chemotherapy and that SIL-2R may distinguish active immunity from immunologic memory to this infection.