Three case reports of intrauterine herpes simplex virus infection (HSV) and 61 cases published between 1963 and 2009 are reviewed by researchers at Baylor College of Medicine, Houston, TX. HSV was cultured in 54 (84%) cases (HSV2 from 36 and HSV1 from 10). Diagnosis was established by PCR, and/or immunohistochemistry. The typical triad of symptoms (cutaneous, CNS, and ophthalmological) occurred in 19 (30%) cases. Cutaneous and CNS manifestations without eye findings occurred in 22 (34%) infants while cutaneous and eye disease without CNS involvement was uncommon (6 [9%] cases). Isolated cutaneous manifestations occurred in 14 (22%) cases. Two (3%) infants had CNS disease alone. Of 43 (67%) with CNS manifestations of intrauterine HSV infection, 29 had more than one neurologic finding, and 25 (39%) had ocular findings, including 18 with retinal disease. The frequency of neurologic abnormalities in decreasing order included calcifications in 19 (44%), porencephaly/encephalomalacia in 16, ventriculomegaly 13, microcephaly 10, hemorrhage 8, and seizures in 7. In the authors’ cases, hydrocephalus on fetal ultrasound, neonatal microcephaly, ventricular enlargement, porencephaly, intracranial calcifications adjacent to the third ventricle, optic atrophy and choreoretinitis were listed. CSF in case 1 contained 5 WBC/mm3, 6000 RBC/mm3, protein 189 mg/dL, and glucose 37 mg/dL. Case 2 had a hemorrhagic infarct on CT, and CSF was unremarkable. Case 3 at birth had bulging fontanelles, split cranial sutures, and impaired primitive reflexes. No skin lesions were present. CSF revealed 178 WBC/mm3, 790 RBC/mm3, protein 1458 mg/dL, and glucose of 20 mg/dL. Transcranial ultrasound showed hydrocephalus ex vacuo and encephalomalacia. CT showed absent cerebellar hemispheres, hypoplastic cerebral hemispheres, and calcifications. Eye exam showed choreoretinitis and vitreal hemorrhages.