Dendritic keratitis occurred during oral acyclovir (ACV) therapy in a 60-year-old man. Corneal stromal edema and iritis were found at his first visit. Herpetic keratouveitis was suspected, based on clinical findings and previous history. Treatment with steroid eyedrops and ACV ointment was initiated. However, ACV [corrected] ointment was changed to oral ACV, since conjunctival ulcer occurred as an adverse effect of the ointment. Subsequently, he received long-term oral ACV medication and steroid eyedrops for recurrent keratitis. The fifth recurrence was also treated with oral ACV and steroid eyedrops. At this time, although the stromal keratitis had improved, there was an outbreak of dendritic keratitis. The lesion healed spontaneously after only a reduction in the steroid. The 50% effective dose (ED)50 of the isolated virus to ACV was 4.4 +/- 0.15 micrograms/ml (mean +/- SD), a level considered ACV-resistant in vitro. The clinical course of this case emphasizes that it is important to consider the route and duration of ACV administration and the use of steroids in the treatment of stromal keratitis or keratouveitis.