The adrenal gland has been known to be a common site of opportunistic infections and tumors that define the acquired immunodeficiency syndrome (AIDS) ever since the first autopsy data were published. We have examined the adrenal glands of 66 AIDS patients autopsied in New York City and tabulated and graded the findings in an attempt to estimate the likelihood of adrenal insufficiency developing on the basis of these lesions. AIDSdefining conditions were found in the adrenal glands of 56% of patients, primarily opportunistic infections (53%) and much less frequently neoplasms (3%). Cytomegaloviral (CMV) infection was by far the most common type (42%), followed by mycobacterial (8%) and fungal infections (3%). There was one case eachof Kaposi’s sarcoma and lymphoma. Total necrosis of adrenal cortex was restricted to 2 cases of tuberculosis. CMV adrenalitis, although the most common infection and often associated with necrosis, never resulted in more than 30% destruction of the cortex. We conclude that although histopathological evidence of adrenal disease is common in AIDS, most such lesions are not sufficiently extensive to result in adrenal insufficiency. In contrast to previous reports stressing the importance of CMV adrenalitis as a possible cause of adrenocortical insufficiency, we now find tuberculosis the more likely cause of total cortical destruction.