T-cell apoptosis and anergy as possible causes of impaired antigen specific responses and their subpopulation targets in patients with pulmonary tuberculosis were investigated. A decrease in PPD-stimulated proliferative responses were revealed in 43% of the examinees. The impaired PPD response was shown to be associated with both increased lymphocytic apoptosis and the arrest of cell cycle progression. CD4 and CHD8 T cells underwent apoptosis in PPD-stimulated cultures. Whereas a moderate apoptosis of CD4 cell could occur in PPD-reactive patients, accelerated apoptosis of CD8 cells developed only in PPD-unresponsive group. Both T-cell subpopulations displayed a decreased count of cells in S,G2/M phases of a cell cycle. Similar to apoptosis, the anergy of CD8 T cells was typical of PPD-unresponsive patients. Elevated apoptosis and anergy of CD4 and CD8 T cells in vitro were accompanied by a decline in the proportion of T cells and their subpopulations in patients with impaired PPD responses.