Cytomegalovirus (CMV) infection after heart transplantation (HTx) is a severe complication, which leads to long treatment and hospital stay. Even if prophylactic therapy with anti-CMV IgG antibodies is performed, there is a high incidence of infection, especially when the heart from a CMV positive donor is transplanted to a CMV negative recipient (high risk constellation). This study evaluates the prophylactic antiviral therapy with ganciclovir in CMV high risk constellation at HTx. Out of 108 HTx, 29 CMV negative recipients (IgG and IgM) received a heart from a CMV positive donor (IgG pos., IgM neg.). The control group (CO) (n = 8) was treated with anti-CMV IgG antibodies (Cytotect 2 ml/kg at day 0, 1, 2, 7, 14, 21,), whereas the study group (GAN) (n = 13) was treated with ganciclovir (7.5 mg/kg single dose n = 8, or 5 mg/kg in twice daily doses n = 5 from day 1 to 14). Urea, creatinine, white blood cell count and platelet count was controlled daily. No side effects on renal and bone marrow function were noted. Therapy was well tolerated. Both groups had similar immunosuppressive protocol (prophylactic cytolysis, prednisone, azathioprine and cyclosporin A) and were similar in age, sex, preoperative diagnosis and NYHA class. Seroconversion for CMV (IgM and IgG) was observed in 75% of CO and 31% of GAN (p less than 0.05). Clinical manifestations of CMV infection started in the second month after HTx with fever in both groups CMV-organ manifestations developed in 50% (or 67% of infected) in CO (enterocolitis 2, pneumonitis 3, tonsillitis 1), and in 15% (or 50% of infected) in GAN (pneumonitis 2, epididymitis 1) NS.(ABSTRACT TRUNCATED AT 250 WORDS)