Six infants with disseminated HSV had no mucocutaneous lesions at any time during the course of the illness. These infants presented with lethargy, poor feeding, apnea, acidosis, and hepatomegaly. The diagnosis of HSV was made by culturing the infant's oropharynx and blood, and the maternal cervix. Eight infants with HSV encephalitis had no skin, eye, or mucous membrane lesions. These infants presented with lethargy and low-grade fever, followed within 24 hours by the onset of focal partial motor seizures. The seizures were refractory to anticonvulsant therapy. The mean CSF white cell count was 131 cells/mm3;the glucose and protein concentrations were in the normal range. Brain biopsy was required for the early diagnosis of HSV encephalitis. These 14 cases presented 70% (14/20) of all infants with neonatal HSV diagnosed during the study period. HSV infection should be considered in infants with no mucocutaneous lesions who have signs usually associated with bacterial sepsis or who develop focal seizures during the first three weeks of life.