A 71-year-old man presented with herpes zoster ophthalmicus and ocular involvement. Following the institution of intravenous therapy with acyclovir, the patient developed fever, hemoptysis, and a pleural friction rub. A ventilation-perfusion lung scan showed no defects; roentgenograms showed bilateral infiltrates and a left-sided pleural effusion. The fever abated promptly following discontinuation of acyclovir, and radiographic abnormalities resolved over ten days. No other anti-infective therapy was given. To our knowledge, the syndrome of fever, pulmonary infiltrates, and pleural effusion following use of acyclovir has not been previously reported.