Eight patients with brain biopsy-proven herpes simplex encephalitis were seen at the Massachusetts General Hospital, Boston, within a three-month period in the summer of 1977. The unusual temporal clustering of these cases engendered a formal epidemiologic investigation. No significant link among these patients was uncovered, and analysis of the cleavage products of seven of the eight viral isolates produced by the restriction endonucleases HsuI and HpaI showed that they were different. This cluster thus appears to have been a random event. Its occurrence, however, emphasizes that herpes encephalitis is not a rare disease in this country. In addition, the utility of restriction enzyme cleavage of DNA in clarifying the epidemiology of viral disease is underscored.