The cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4⁺ and CD8⁺ lymphocyte numbers, and the activation plus memory/naïve phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD⁻), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4⁺ lymphocyte number of the TBC group was lower than the PPD^– group (P < 0·05). This difference was apparently lost after treatment. The higher and the lower number of naïve T CD4⁺ cells was observed in the PPD^– and TBC group, respectively. CD8⁺ T lymphocytes were also statistically different among the four groups (P = 0·0002), lower in the TBC group (P < 0·05). CD8⁺ T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. The percentage distribution of these markers was statistically different between the four groups (P = 0·0055). TBC patients had a higher percentage of CD38⁺ cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naïve, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis.