Summary Examination of brain tissue taken at autopsy from a 55-year old male showed the presence of herpes simplex viral antigen by immunofluorescence techniques. A suspension of this tissue was inoculated into cultures of human diploid fibroblasts. After 72 h, viral particles at different stages of development were seen inside the nuclei. Envelopment of the viral particles seemed to occur in association with the nuclear membranes, endoplasmic reticulum, cytoplasmic vacuoles and plasma membranes. Severely altered nuclear membranes, with as many as 4 to 8 layers of nuclear envelope, emphasized the common occurrence of membrane reduplication associated with herpes simplex infection. Unusual membrane-bound, dense, rounded inclusions, 100 to 500 nm in diameter, were present in the nucleus. These inclusions apparently were formed between the inner and outer lamellae of the nuclear membrane.