Twelve of 17 patients with cytomegalovirus infections (two with mononucleosis, five with disseminated infection and immunosuppression, and five congenitally infected infants) were treated with 5–20 mg of adenine arabinoside (ara-A) / kg intravenously for six to 18 days. Infants and patients with mononucleosis had higher titers of cytomegalovirus in urine before treatment and more prolonged urinary viral suppression after treatment than immunosuppressed patients. However, a quantitatively lesser viruria returned after one to three weeks in all patients. During therapy in immunosuppressed patients, urinary excretion of cytomegalovirus was only slightly reduced, with persistent viremia. Clinically, two infants and two patients with mononucleosis improved; no immunosuppressed patient improved. No significant clinical toxicity to the liver, kidney, or bone marrow occurred in treated patients. An untreated group of three immunosuppressed patients and two with mononucleosis had persistent viremia and viruria. The results suggest that a subtoxic dosage of ara-A suppresses urinary excretion of cytomegalovirus in man. The poor response in immunosuppressed patients may be due to the severity of immunosuppression, individual variation in metabolism of ara-A, the presence of concurrent infections, or, possibly, specificity of cytomegalovirus strains.