Cytomegalovirus (CMV) infection is still a problem for organ transplant recipients despite studies that long-term prophylaxis with high dose of acyclovir or ganciclovir given to all organ recipients may limit the consequences of infection and disease. In the present report of 160 consecutive renal transplant patients, we used a diagnostic assay for CMV antigenemia (detection of CMV antigen in peripheral blood leukocytes) and treated with ganciclovir only those patients who had a positive test. No patient in this series had routine prophylaxis. Out of 160 patients, 71 had clinical and/or laboratory signs of infection, and were tested for early antigen in peripheral leukocytes. The test was positive in 35, all of whom received a course of 3 wk ganciclovir treatment which effectively cured CMV in 34 count of 35. One patient was ganciclovir-resistant, but responded to foscarnet. None of the 36 patients who had no early antigenemia and did not receive treatment developed the disease. The treatment was extremely well tolerated in all our patients with no adverse events. Thus, even though this was not a controlled study, our present results may be taken to indicate that long-term acyclovir or ganciclovir for all organ transplant recipients might be no longer totally justified. We conclude that detecting viral antigen in circulating leukocytes identifies patients who are indeed at risk of developing severe CMV disease. When these patients are treated early enough, CMV is eliminated with a relatively short course of ganciclovir, which has virtually no side effects.