The increasing importance of the acquired immunodeficiency syndrome (AIDS) as a cause of large, clinically significant pericardial effusions has not been well documented. To determine the frequency and characteristics of large AIDS-associated pericardial effusions, we reviewed the records of 50 consecutive patients undergoing pericardiocentesis between 1985 and 1990; AIDS was the most common underlying illness and was present in 14 patients (28 percent). The pericardial fluid was diagnostic in three (21 percent) of the 14 cases (one bacterial, one positive for acid-fast bacilli, and one lymphoma). Of the 11 patients with nondiagnostic fluid, one underwent a pericardial biopsy which revealed granuloma consistent with mycobacterial disease, four had active pulmonary tuberculosis (TB), and two responded clinically to anti-TB therapy. Thus, in 8 (57 percent) of the 14 patients with AIDS, there was either definitive or suggestive evidence of mycobacterial disease. We conclude that AIDS is now a common underlying illness associated with large pericardial effusions and that mycobacterial disease may frequently be the etiology.