Patients with newly diagnosed active pulmonary tuberculosis were divided into high and low responder groups on the basis of 3H-thymidine incorporation of peripheral blood mononuclear cells (PB MNC) induced by tuberculin-purified protein derivative (PPD). The group of patients with low tuberculin responses was characterized by anergy to tuberculin skin testing and larger numbers of circulating monocytes than the high responders. The groups were comparable in the extent of pulmonary tuberculosis and other clinical parameters. PB MNC from tuberculin low responders had normal phytohemagglutinin (PHA) but depressed streptokinase-streptodornase (SKSD), Candida antigen, and tetanus toxoid-induced 3H-thymidine incorporation. Depletion of adherent cells resulted in a mean 24.4-fold enhancement of T lymphocyte responses to PPD in the low responders as compared to a 2.9-fold increase in the high responders. The low response of PB MNC from low responders to nonmycobacterial antigens was not similarly augmented by adherent cell depletion. Adding back graded numbers of adherent cells to purified T lymphocyte populations resulted in greater depression of the PPD-induced proliferative response to the tuberculin low responders when compared to the high responders. These studies provide evidence for circulating suppressor adherent cells in tuberculosis patients with diminished responsiveness to PPD in vitro. This immunosuppression is not mediated by adherent cell supernatant products, nor does it involve T lymphocyte labile during culture. However, complex cellular interactions, possibly involving suppressor T cells, are implicated by the restriction of this phenomenon to PPD-induced lymphocyte activation and the depression of the PB MNC responses to nonmycobacterial antigens. The suppressor adherent cells defined in these studies may be relevant as a cause or consequence of infection in a subset of patients with tuberculosis.