Five patients with acquired immunodeficiency syndrome (AIDS) and presumed varicella-zoster virus retinopathy had recurrence of retinopathy after stabilization with initial intravenous antiviral therapy. Recurrences were recognized as increased retinal opacification at the borders of preexisting lesions or as new lesions. In four of the five patients, recurrences were temporally associated with a reduction in the amount of antiviral medication being received. Changes included switch from intravenous to oral acyclovir (two patients), taper of oral acyclovir (one patient), and discontinuation of medications (one patient). In four patients disease was initially unilateral; in three of these four, disease subsequently developed in the previously unaffected fellow eye at the time of recurrence. The median time from stabilization of disease to recurrence was 51 days (range, 14 to 90 days). In contrast to the management of varicella-zoster virus retinopathy in immunocompetent patients and varicella-zoster virus lesions of the skin, varicella-zoster virus retinopathy in patients with AIDS appears to require chronic suppressive antiviral therapy to prevent recurrences. In this respect it is similar to other opportunistic retinal infections in patients with AIDS. The best drugs and optimal treatment regimens for maintenance antiviral therapy remain unknown.