Herpes simplex virus (herpesvirus) was isolated from autopsy lung specimens of 20 patients with clinical, roentgenographic, and histologic evidence of pneumonia. Mucocutaneous herpesvirus infection preceded the onset of pneumonia in 17. Twelve patients had focal pneumonia, 10 of whom had concomitant herpetic tracheitis, esophagitis, or both. Eight patients had diffuse interstitial pneumonia, six of whom had dissemination of herpesvirus to the other organs. Of the eight lung isolates available for typing, seven were herpesvirus-1 and one, herpesvirus-2. A high prevalence of herpesvirus antibody in serum samples obtained before pneumonia and identical restriction endonuclease patterns between mucosal and lung isolates in individual patients indicated that, in most cases, herpesvirus pneumonia was due to endogenous reactivation of virus. Focal herpesvirus pneumonia appeared to result from contiguous spread of herpesvirus to lung parenchyma, whereas diffuse interstitial pneumonia appeared to be a manifestation of hematogenous dissemination of virus.