A retrospective review of adenovirus infections at Texas Children's Hospital during 1990-1996 was performed to evaluate the epidemiology, clinical course, management, and outcome of disseminated adenovirus disease (DAD) in children. DAD with multiorgan involvement occurred in 11 (2.5%) of 440 adenovirus-infected patients. Six (54%) of the 11 were immunocompromised and 5 (45%) were immunocompetent. Mortality was 83% among the immunodeficient, 60% in the immunocompetent, and 73% overall. Two (28%) of the 7 patients receiving immunoglobulins with or without antivirals and 3 (75%) of the 4 not treated died of DAD. DAD was caused by particular serotypes (3, 5, and 7) and occurred at a younger age in immunocompetent children. Viremia and prolonged viral excretion were more common in the immunocompromised. Clinical features and outcome were similar in both groups. Prospective studies addressing the use of new antiviral agents, combination antiviral therapy, and preventive strategies are necessary to determine the optimal therapeutic approach for patients with DAD.