The present study concerns the effect of hydrocortisone (HC) on the effector functions of Bacillus Calmette Guerin-purified protein derivative (BCG-PPD)-activated macrophages. Such activated macrophages release greater amounts of H2O2 and NO2-, inhibit the intracellular proliferation of T. gondii and kill L. monocytogenes more efficiently than resident macrophages. This activation was not fully expressed by macrophages from BCG-activated mice that had received a subcutaneous injection of HC 2 days before intraperitoneal injection of PPD, since the inhibition of the intracellular proliferation of T. gondii, the release of NO2- and the rate of intracellular killing of L. monocytogenes were lower than in macrophages from BCG-PPD-activated mice. However, treatment with HC did not impair the release of H2O2 by BCG-PPD-activated macrophages. The results show that the treatment of infected mice with HC inhibits their ability to develop adequate intracellular microbicidal mechanisms.