Literature has shown that immunosuppression observed in systemic mycosis can be related to damage in primary lymphoid organs. We have studied the immunopathological alterations induced experimentally by Paracoccidioides brasiliensis in these organs. In this work, thymic alterations induced in BALB/c mice during acute and chronic stages of infection are described. It was observed that P. brasiliensis is able to invade the thymic microenvironment, inducing severe atrophy characterized by degeneration of the cortical area, organ weight decrease, loss of corticomedullary delimitation and increase in histiocyte number. Occurrence of polymorphonuclear infiltration in the subcapsular area was also observed. Our results demonstrate that P. brasiliensis induces profound thymic atrophy and raises the question of whether this could be a fungal strategy to achieve successful establishment in the host over the long term.