Herpes simplex encephalitis developed in a patient with Hodgkin's disease under therapy. Despite treatment with idoxuridine in a total dose of 280 mg/kg intravenously, he died without showing any clinical response. At autopsy, there was no gross or microscopic evidence of Hodgkin's disease, and virus isolated from the brain postmortem was inhibited in vitro by idoxuridine 0.5 mug/ml. Failure of idoxuridine to affect the course of infection by a drug-sensitive virus may be due to poor tissue penetration, although the role of the Hodgkin's disease cannot be discounted.