We here report a 32-year old homosexual man with AIDS who had an abnormal ACTH stimulation test while taking megestrol actetate (megace). On further evaluation, he was found to have recurrent Non-Hodgkin lymphoma (spleen) and intracranial toxoplasmosis, perhaps imitating or aggravating symptoms suggestive of adrenal insufficiency (AI). We diagnosed secondary AI due to megace treatment and tapered this medication under simultaneous hydrocortisone replacement therapy. After the patient's intracranial toxoplasmosis had been treated with intravenous bactrim, his symptoms disappeared. We conclude that patients with AIDS on megace therapy should receive special attention in regards to the potential development of AI, especially in stress situations such as infections or pain.