The objective of this study was to evaluate the influence of protease inhibitor therapy on the rate of progression and survival of 17 AIDS patients with stable Cytomegalovirus retinitis, who were receiving anti-CMV therapy. CD4+ count, HIV load, and CMV antigenemia assay were determined at baseline, at the first month, and every 3 months thereafter. Median CD4+ count increased from 11 to 87 cells/mm3, and median HIV RNA level decreased from 4.96 to 3.28 log10 copies/ml, after 6 months on therapy. Although 9 patients (53%) relapsed in a median time of 97 days (range, 15-152 days), no further episodes were observed during a median follow-up of 17 months (range, 5-18 months). Thus, the probability of remaining free of relapse was twofold higher than that observed in matched patients who did not receive protease inhibitors. Median CD4+ count at the 3rd month was higher in those individuals who went on to progress (p = .03), and a positive result to a CMV antigenemia test was associated with progression of retinitis (relative hazard, 4.45; p = .04). Survival rate was 94% at 17 months (89% increase). Therefore, protease inhibitor therapy reduces retinitis progression and improves survival. However, the immunologic response may not provide initial sufficient protection to avoid, or even may play a role on, early CMV progression.