Heart muscle disease in the acquired immune deficiency syndrome (AIDS), characterized by electrocardiographic changes or congestive cardiomyopathy, is a documented clinical problem, but its pathogenesis is obscure. In AIDS the heart is known to be involved by a variety of opportunistic infections as well as Kaposi's sarcoma, but no causative relation with the development of cardiomyopathy has been established. This study reports evidence for direct infection of the heart in AIDS, not by an opportunistic pathogen but by the AIDS, not by an opportunistic pathogen but by the AIDS virus itself, the human immunodeficiency virus (HIV). For this study the technique of in situ deoxyribonucleic acid hybridization was applied to cardiac tissues obtained at autopsy from AIDS patients. Using sulfur-35-labeled ribonucleic acid probes encompassing the entire HIV genome, HIV nucleic acid sequences were detected in cardiac tissue sections from 6 of 22 patients examined who died of AIDS. The hybridization targets appeared to be cardiac myocytes, although their precise morphology was often obscured by the intensity of the signal. The myocardial cells showing a positive hybridization signal were sparse, often comprising only 1 or a few cells per section, and their number and location did not correlate obviously with any histopathologic or clinical evidence of heart muscle disease in these patients. It is conceivable that the presence of HIV nucleic acid sequences may represent a preclinical marker of impending AIDS-associated heart muscle disease. This sequela would not be recognized in many patients, including those in this series, who died rapidly of Pneumocystis carinii pneumonia, Kaposi's sarcoma and other well-documented manifestations of AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)