Background Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB. In this study, we obtained blood samples from 114 Chinese pediatric TB patients and 116 matched controls to study the association of phenotypic subsets of peripheral lymphocytes with different clinical phenotypes of TB. Methods The subjects were classified as the control group and the TB patients group which were further divided into a pulmonary TB group and an extra-pulmonary TB group (more serious than the former). The distribution of lymphocyte subpopulations, including T lymphocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes, B lymphocytes, and natural killer (NK) cells, were quantitatively analyzed by flow cytometry. Results Compared to the healthy controls, TB infection was associated with significantly higher B cell (P <0.0001), and lower T cell (P=0.029) and NK cell (P <0.0001) percentages. Compared to pulmonary TB patients, extra-pulmonary TB was associated with relatively higher B cell (P=0.073), and lower T cell percentages (P=0.021), higher purified protein derivative (PPD) negative rate (P=0.061), and poorer PPD response (P=0.010). Most pulmonary TB cases were primary pulmonary TB (89.1%), and most extra-pulmonary TB cases had TB meningitis (72.1%). Conclusions This study demonstrates changes in the lymhocyte distribution in children suffering from different clinical phenotypes of TB; such as primary pulmonary TB, and TB meningitis. These patterns may have significance in understanding the pathogenesis and prognostic markers of the disease, and for developing immunomodulatory modalities of therapy. Chin Med J 2012;125(2):275-280