One hundred twenty-four patients underwent heart transplantation over a 3-year period. All patients were monitored for human cytomegalovirus (CMV) infection if at risk for primary CMV infection or in the presence of CMV-related symptoms. Rapid diagnosis of CMV infection relied on virus isolation and identification or viral antigen detection by using monoclonal antibodies to CMV immediate early or early antigens. In addition, "in situ" hybridization was used to detect viral DNA in tissue samples. Specimens examined included peripheral blood polymorphonuclear cells for CMV viremia and antigenemia determination, together with the most appropriate clinical samples when organ involvement was suspected. There was a 100% (6/6 patients) incidence of primary CMV infection in seronegative recipients of hearts from seropositive donors, whereas no CMV infection occurred in the three seronegative recipients receiving a transplant heart from CMV-negative donors. CMV hyperimmunoglobulin prophylaxis did not prevent primary CMV infection. Five of the six patients with primary CMV infection were symptomatic. In addition, 15 patients (13%) had symptomatic recurrent CMV infection. The most frequent symptoms associated with CMV infection (either primary or recurrent) were fever (19 patients) and pneumonia (eight patients). CMV viremia was detected in 17 patients either before or concomitantly with the appearance of fever. CMV was isolated from bronchoalveolar lavage in all cases with pneumonia; however, another pathogen was associated with CMV and appeared to be the major cause of pneumonia in 75% of these patients (6/8). Twelve patients (five with primary and seven with recurrent CMV infections) were treated with ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)