In healthy individuals the substantial lymphocytosis during a bout of exhausting exercise constitutes primarily mature T cells from the peripheral lymphoid organs but naïve T cells are also recruited. This study investigated whether the defective CD4 + T-lymphocyte count in peripheral blood during rest in human immunodeficiency virus (HIV)-infected patients would also be observed following a maximal output ergometer bicycle test. At rest, in 45 well-treated HIV-infected patients, mature and naïve CD4 + T-lymphocyte counts were decreased whereas the less immune active CD8 + T lymphocytes were increased compared with 10 healthy control subjects. In response to exercise mature and naïve CD4 + T lymphocytes increased less and mature and naïve CD8 + T lymphocytes increased most in HIV-infected patients. In conclusion, defective resting mature and naïve CD4 + T lymphocytes in well-treated HIV-infected patients are also reflected in defective acutely mobilized active immune cells following exhausting exercise. The CD4 + T-lymphocyte count is highly sensitive to physical activity.