Abstract A 38-year-old man who underwent corneal transplantation in 1973 for treatment of a keratoconus is described. In 1982, hairy cell leukemia was diagnosed and he was treated with splenectomy followed by chlorambucil and androgen therapy. In April 1984, treatment with alpha-2 interferon was begun, and two weeks later, evidence of acute corneal allograft rejection developed. The allograft rejection responded to temporary discontinuation of alpha-interferon and the administration of topical corticosteroid. Treatment with interferon was resumed, and he has subsequently had no clinical evidence of rejection. Although the mechanism of antineoplastic activity of alpha-interferon in hairy cell leukemia is unknown, the observations described in this report suggest that clinically important immune phenomena may occur in patients undergoing interferon therapy.