We describe a 42-year-old man with human immunodeficiency virus infection who developed multiple recurrences of cytomegalovirus (CMV) retinitis despite receiving highly active antiretroviral therapy and having apparent immune reconstitution as evidenced by CD4(+) T lymphocyte counts of > 200 cells/mm(3). Laboratory investigation during one recurrence of retinitis confirmed that there was active CMV replication in the plasma and vitreous fluid. In addition, lymphoproliferative responses to CMV antigens were absent despite evidence of reactivity to Candida antigen and pokeweed mitogen. The clinical significance of this case and of other recently reported cases is discussed.