Intestinal perforation is an extremely uncommon complication of Mycobacterium tuberculosis (MTB) infection. We describe two cases of multiple intestinal perforations secondary to MTB in individuals infected with the human immunodeficiency virus (HIV) presenting at the Los Angeles County-University of Southern California Medical Center over a 2-month period. For each case, this was the first presentation of AIDS. One of the two patients had concurrent pulmonary involvement. One patient died, and the other responded to therapy and was discharged in stable condition. The most striking finding in both cases was the extremely large number of acid-fast bacteria seen transmurally on the pathological specimens. This might be related to impaired T-cell function. The resurgence of MTB infection in North America, in the presence of the AIDS epidemic, may result in an increasing frequency of unusual presentations, such as intestinal perforation. Intestinal perforation due to MTB should be considered in HIV-infected patients presenting with an acute abdomen.