Thirty-seven consecutive cases of cardiac tamponade occurring over a 6-year period were retrospectively studied from January 1986 to December 1991 in an inner-city public teaching hospital. All episodes were secondary to medical illnesses. Thirteen (35 percent) of 37 patients had HIV infection. Significant differences (HIV vs non-HIV) in clinical presentation were noted in the following parameters: (1) age (34 +/- 7 years vs 56 +/- 14 years, p < 0.001); (2) febrile presentation (62 percent vs 17 percent, p < 0.02); and (3) presence of pulmonary infiltrates (54 percent vs 17 percent, p < 0.03). All but two patients underwent pericardiocentesis or had operative creation of a pericardial window. Two patients had purulent pericarditis; two patients had tuberculous pericarditis. In the remaining patients, there was no evidence of opportunistic infection or malignancy based on cultures of pericardial fluid and histopathologic analysis of tissue. Six of 13 patients with HIV infection survived to be discharged from the hospital following hospitalization for the illness. We conclude the following: (1) HIV infection is frequently found in patients with cardiac tamponade at inner city hospitals; (2) when young patients present with cardiac tamponade, the coexistence of fever and pulmonary infiltrates is suggestive of underlying HIV infection; and (3) the etiology of the pericardial effusion is not confirmed in the majority of patients with HIV infection.