OBJECTIVES: The purpose of this study was to characterize the histologic and immunopathologic results of 37 endomyocardial biopsy samples from patients infected with human immunodeficiency virus type 1 (HIV-1) who were evaluated for unexplained global left ventricular dysfunction. BACKGROUND: Recent studies have identified a growing number of patients infected with HIV-1 who develop unexplained left ventricular dysfunction and congestive heart failure. Myocarditis has been confirmed at autopsy in small numbers of such patients, although a pathogenic opportunistic infectious agent can rarely be identified. METHODS: All patients had moderate to severe global left ventricular hypokinesia on two-dimensional echocardiography. Endomyocardial biopsy samples were evaluated by standard histologic studies, immunoperoxidase staining and in situ hybridization for cytomegalovirus and HIV-1 gene sequences. RESULTS: Twenty-eight patients presented with New York Heart Association functional class III or IV congestive heart failure. Four patients had myocarditis secondary to known etiologies (opportunistic infection n = 2; drug-induced hypersensitivity myocarditis n = 2). Of the remaining 33 samples, 17 (51%) showed histologic evidence of idiopathic active or borderline myocarditis. Immunohistologic findings revealed induced expression of major histocompatibility class I antigen on myocytes and increased numbers of infiltrating CD8+ T lymphocytes. Specific hybridization within myocytes was observed in 5 of 33 samples with the HIV-1 antisense riboprobe and in 16 of 33 samples with the cytomegalovirus immediate early (IE-2) antisense riboprobe. All but one patient with specific myocyte hybridization presented with congestive heart failure; all patients had myocarditis and CD4+ cell counts < 100/mm3. CONCLUSIONS: This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.