Seventeen patients (ten women and seven men, 23 to 72 years old) with stromal herpetic disease were treated with topical and oral acyclovir for 14 days. Of the 12 patients with disciform edema, five showed minimal improvement, four showed no change, and three showed worsening of their disease. Of the five patients with necrotizing stromal keratitis, one improved, one showed no change, and three became worse. The patients who had been treated with corticosteroids previously had a statistically significantly worse outcome than those who had not been so treated. One patient with necrotizing stromal keratitis showed virus particles in tissue specimens obtained by superficial lamellar keratectomy. Thus, acyclovir was not effective in the treatment of disciform edema or necrotizing stromal keratitis. Further studies are needed to ascertain whether the drug is therapeutically ineffective or whether acyclovir did not reach the stroma in amounts sufficient to affect the course of stromal disease in the human eye.