The presence of human cytomegalovirus DNA was investigated in 103 unfixed endomyocardial biopsies, performed during the first 4 months in 17 heart transplant recipients by polymerase chain reaction. Results were correlated with human cytomegalovirus systemic infection, as detected by the test for the viral lower matrix phosphoprotein pp65 (antigenemia) and by polymerase chain reaction for viral DNA in blood leukocytes (DNAemia). Three patients out of 17 did not develop cytomegalovirus infection and 14 did: 5 had symptomatic disease treated with ganciclovir and 9 developed asymptomatic infection and were not treated. Viral DNA was detected in 24 out of 103 biopsies (23%) from 13 patients: 5 with symptomatic infection during the acute phase of disease (mean levels of pp65: 125+/-232 pp65 positive leukocytes/200,000 examined cells) and 8 patients with asymptomatic infection when the mean antigenemia was 5+/-15/200,000 (4 patients) or when DNAnemia was present in the blood (4 patients). No histological evidence of myocarditis was shown in viral DNA-positive biopsies. No difference in acute rejection was found in viral DNA-positive and DNA-negative biopsy specimens in symptomatic and asymptomatic infected patients. Our experience suggests that during systemic symptomatic and asymptomatic cytomegalovirus infection, polymerase chain reaction can detect a relatively frequent myocardial involvement, but this involvement is not associated with myocarditis or with a higher incidence of acute rejection. THe presence of viral DNA in myocardial biopsies can be a result of high viremia, but it also can be due to low level of viral DNA in circulating infected leukocytes. Polymerase chain reaction is the most sensitive method for cytomegalovirus DNA detection in biopsies, but its results need to be evaluated together with morphology-preserving methods and systemic markers of infection in order to make a correct diagnosis.