SUMMARY:The myocardium may be the target of several types of viral infections. The importance of hepatitis C virus (HCV) infection has been recently noted in patients with myocarditis and in patients with dilated or hypertrophic cardiomyopathy. The present study sought to detect HCV genomes in formalin-fixed paraffin sections of autopsied hearts from patients with myocarditis and patients with dilated or hypertrophic cardiomyopathy. Paraffin sections were deparaffinized, RNA was extracted, and the positive and negative strands of HCV RNA were detected by performing reverse transcription and nested polymerase chain reaction. The polymerase chain reaction products were cloned and sequenced. -actin gene was used as a control for the successful amplification of a housekeeping gene. Among 106 hearts examined, -actin gene was amplified in 61 hearts (57.5%). Among the latter, HCV RNA was detected in 13 hearts (21.3%), and negative strands in 4 hearts (6.6%). HCV RNA was found in 4 hearts (33.3%) with myocarditis, in 3 hearts (11.5%) with dilated cardiomyopathy, and in 6 hearts (26.0%) with hypertrophic cardiomyopathy. The sequences recovered from nine patients were highly homologous to the standard strain of HCV. HCV genomes were not found in either 35 hearts from patients with myocardial infarction or 20 hearts from patients with noncardiac diseases. These HCV RNA positive samples were obtained from 1 heart in 1979, 7 hearts between 1980 and 1989, and 5 hearts since 1990, indicating that HCV RNA can be amplified from paraffin-embedded hearts preserved for many years. This method of detecting HCV genomes in formalin-fixed paraffin cardiac specimens has enabled us to widen our research into HCV infection and has been helpful in identifying the presence of HCV infection in cardiac myopathic disorders. (Lab Invest 2000, 80:1137-1142.