Because tuberculosis (TB) is primarily a pulmonary disease, we examined the cytokine responses of CD4(+) T lymphocytes in bronchoalveolar lavage (BAL) fluid after incubation with purified protein derivative (PPD) in human immunodeficiency virus-negative patients with TB and control subjects with nontuberculous respiratory disease. Parallel blood and BAL fluid samples from each subject were incubated with or without PPD, and the proportions of CD4(+) T lymphocytes producing interferon (IFN)-gamma or tumor necrosis factor (TNF)-alpha were measured by flow cytometry. The proportions of PPD-activated IFN-gamma- and TNF-alpha-producing CD4(+) cells were low among control subjects (median, 0.33% and 0.78%, respectively). By contrast, among patients with TB, strong IFN-gamma and TNF-alpha responses were demonstrated (median, 24.0% and 32.4%, respectively), regardless of whether the TB was pulmonary or nonpulmonary. Measurement of type 1 cytokine production by CD4(+) T lymphocytes in response to PPD in BAL fluid is a promising new diagnostic test for active TB in immunocompetent individuals.