Oxygen keeps the entire enzymatic machinery in its physiological state. Senescence is associated with damage caused by oxidative stress, affecting also the immune system. In this study the effect of chronic hypoxia for 12 days on young and elderly rat thymus was investigated. The significant changes in cell thymic organization in young and old-aged rat thymus, with redistribution of thymic cells and stroma, were even more marked after prolonged hypoxia. These were further associated to down-regulation of NF-kappaB expression in young rats but up-regulation in old rats. Reorganization of thymic compartments together with disregulated expression of transcription factors, mainly expressed by 'common' thymocytes, may be related to an altered function under hypoxic conditions, inducing opposite responses in young and aged thymuses, probably related to different states of basal oxidative stress.