Four new cases of neonatal herpes pneumonia and five cases from the literature were assessed. Clinical presentations, laboratory abnormalities, and radiographic features were analyzed in an effort to establish helpful criteria for early institution of antiviral therapy. Any neonate who develops respiratory distress between the third and 14th days of life and has a chest radiograph that reveals prominent hilar with a central interstitial infiltrate is at high risk for herpes pneumonia. Antiviral therapy pending antigen detection and culture results should be strongly considered in any such patient when the etiology of pneumonitis is unknown and any of the following is found: (1) thrombocytopenia; (2) evidence of disseminated intravascular coagulation; (3) elevated values in liver function tests; (4) a positive result in a rapid screening test for herpes simplex virus; (5) lymphocytic pleocytosis of the cerebrospinal fluid; (6) development of vesicular skin lesions; or (7) further deterioration in clinical status during treatment with antibiotics.