A 65-year-old man underwent orthotopic cardiac transplantation and was prophylactically treated for cytomegalovirus infection with intravenous ganciclovir. He received standard dosages and had normal renal function. After 6 days of therapy he experienced psychotic symptoms with hallucinations, confusion, and disorientation. His altered mental status resolved after the drug had been discontinued for 5 days. Ganciclovir was suspected as a cause of the symptoms. Alternative etiologies of were explored and excluded.