Exercise affects lymphocytes as reflected in total blood counts and the lymphocyte proliferative response. In addition, the production of immunoglobulins is impaired and during exercise the natural killer cell activity increases followed by suppression in the recovery period. Cardiopulmonary adjustments play a major role in lymphocyte response to physical activity. During intense exercise, the activated sympathetic nervous system increases blood flow to muscle as blood flow to splanchnic organs decreases. After exercise, sympathetic tone and blood pressure becomes reduced. The spleen contains lymphocytes and blood resides in gut vessels. A change in blood flow to these organs could affect the number of circulating lymphocytes. Reduced production of immunoglobulins results from suppressed B-cell function and, in response to exercise, mucosal immunity appears to decrease. Pulmonary hyperventilation and enhanced pressure in pulmonary vessels induce increased permeability of airway epithelium and stress failure of the alveolar-capillary membrane during intense exercise. A physiological perspective is of importance for evaluation of the exercise-induced change in lymphocyte function and, in turn, to post-exercise increased susceptibility to infections.