Recurrent infections could be seen in frequent flyers indicating an impaired immune reaction after long-distance flights. The increase of the concentration of neopterin points to an activation of the cellular part of the immune system. In combination with the altered differential blood counts, the changes in the proliferation rate of lymphocytes and the immune phenotyping the increase of neopterin leads to an explanation of the down-regulation of the immune system after flights. The mild hypoxia on board of an aircraft triggers an increase of catecholamines and cortisol in serum. Catecholamines lead to a shift of leukocytes from different compartments to the circulating blood and to an activation of immune cells. Cortisol triggers the differentiation of a subgroup of T-Lymphocytes with a rise in TH2-helper cells and a down-regulation of TH1-cells. The latter ones are, however, essential for an induction of a reaction of the cellular immune system and so the function of the cellular part of the immune system will be reduced. If no infection occurs, the concentration of neopterin in serum will drop to normal.