A case of herpes simplex virus (HSV) infection was diagnosed by biopsy of the cervix and endometrium in a 28-year-old woman with abnormal uterine bleeding. The cervical biopsy demonstrated surface ulceration and underlying patchy necrosis of endocervical clefts and stroma. The endometrium was late secretory, with striking patchy necrosis of gland epithelium and stromal cells. Both sites contained occasional epithelial and stromal cells with nuclear inclusions consistent with HSV infection. Viral culture further confirmed the presence of HSV. Immunohistochemistry demonstrated the presence of HSV antigens in the tissue, and ultrastructural study of the endometrium revealed viral particles within epithelial and stromal cells. The results suggest endometrial involvement via an ascending infection from the cervix. Recognition of this unusual pattern of endometrial inflammation may facilitate diagnosis of additional cases. © 1989.