Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-␥) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-␥ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-␥ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-␥ immunoreactivities in serum followed kinetics in sputum. TNF-␣, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-␥, however, TNF-␣ and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.Despite efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Obstacles to TB control include the long duration of therapy and the lack of concrete markers indicating success or failure of treatment early during the course of active disease.Sputum culture conversion following 8 weeks of treatment has been used as a surrogate of response to antituberculous chemotherapy (16). However, cultures require up to 6 weeks to perform and, therefore, are not ideally suited for real-time assessment of response to treatment. By contrast, assessment of immunological parameters in biological fluids can be accomplished within days of sample collection and, if validated as a surrogate marker, may be particularly useful in settings where the activity of short-term administration of new drugs (early bactericidal activity studies) or of immunoadjuvants to standard anti-TB therapy is tested. Further, identifying immunological parameters that correlate with culture sterilization may provide important information about host factors most relevant to anti-Mycobacterium tuberculosis (MTB) immunity.Since TB predominantly affects the lung, assessment of specimens recovered from this site may best reflect the interaction between the host and MTB during active disease. Fiber optic bronchoscopy and bronchoalveolar lavage (BAL) has been used to assess anti-MTB immunity in situ (18,19). However, this invasive technique cannot be applied serially during treatment. As a result we investigated alternative approaches for evaluating anti-MTB immune responses ...