We treated 13 eyes of 12 patients with the acute retinal necrosis syndrome (ARN) with intravenous acyclovir (1500 mg/M2/day) for an average of 10.9 days. All patients were also treated with oral aspirin or Coumadin. in an attempt to prevent thrombotic complications and nine of twelve patients were treated with oral prednisone after intravenous acyclovir had been initiated. Regression of retinal lesions was first seen on average 3.9 days after initiation of therapy and required 32.5 days on average for completion. No eye developed new retinal lesions or progressive optic nerve involvement 48 hours or more after initiation of therapy, although progression within the first 48 hours was occasionally seen. Treatment did not ameliorate vitritis or prevent retinal detachment, which occurred in 11 of 13 eyes, an average of 59 days after the initiation of therapy. There were no evident ocular or systemic complications of therapy. Our data suggest the need for a prospective randomized clinical trial to evaluate the efficacy of intravenous or oral acyclovir in the treatment of the acute retinal necrosis syndrome.