This study was conducted to determine the likelihood of the development of a new ocular inflammatory syndrome (immune recovery vitritis, IRV), which causes vision loss in AIDS patients with cytomegalovirus (CMV) retinitis, who respond to highly active antiretroviral therapy (HAART). We followed 30 HAART-responders with CD4 cell counts of >/=60 cells/mm3. Patients were diagnosed with IRV if they developed symptomatic vitritis of >/=1+ severity associated with inactive CMV retinitis. Symptomatic IRV developed in 19 (63%) of 30 patients and in 26 (59%) of 44 eyes over a median follow-up from HAART response of 13.5 months. The annual incidence of IRV was 83/100 person-years. Excluding patients with previous cidofovir therapy did not significantly alter the time course of IRV (P=.79). These data suggest that IRV develops in a significant number of HAART-responders with CMV retinitis and is unrelated to previous cidofovir therapy.