Interleukin (IL)-2 has a central role in regulating T cell responses to Mycobacterium tuberculosis. Adjunctive immunotherapy with recombinant human IL-2 was studied in a randomized, placebo-controlled, double-blinded trial in 110 human immunodeficiency virus-seronegative adults in whom smear-positive, drug-susceptible pulmonary tuberculosis was newly diagnosed. Patients were randomly assigned to receive twice-daily injections of 225, 000 IU of IL-2 or placebo for the first 30 days of treatment in addition to standard chemotherapy. Subjects were followed for 1 year. The primary endpoint was the proportion of patients with sputum culture conversion after 1 and 2 months of treatment. After 1 month, the proportion of patients for whom sputum culture converted to negative was 17% for the IL-2 group compared with 30% in the control group (p = 0.14; chi2). After 2 months, 77% in the IL-2 group were culture negative compared with 85% of those receiving placebo (p = 0.29, chi2). Results were similar when patients with isoniazid monoresistance were included in the analysis. There were no differences in weight gain and no improvement in fever, cough, and chest pain between groups. One patient in each arm relapsed. IL-2 did not enhance bacillary clearance or improvement in symptoms in human immunodeficiency virus-seronegative adults with drug-susceptible tuberculosis.