Human cytomegalovirus (HCMV) causes retinitis and is the leading cause of blindness in patients infected with the human immunodeficiency virus (HIV). While most patients with HIV are HCMV seropositive, not all will develop clinical complications from it. The immune responses that can prevent the development of HCMV retinitis are unknown. The levels of antiHCMV antibodies, induding responses to the two major envelope proteins, gpUL55 (gB) and gpUL75 (gH), which are the targets of neutralizing antibody (NA), were examined in HIV-infected patients with and without retinitis. No specific deficiency in the antibody response of retinitis patients was observed. However, higher levels ofNA were associated with a more favorable clinical course. These results indicate that antibodies may modulate progression of disease, and they suggest a possible role for the exogenous administration of NA in patients who develop HCMV retinitis. © 1995 by The University of Chicago.