Panperitonitis developed in a 57-yr-old Japanese man during the course of Weber-Christian disease (WCD). Emergent operation disclosed three perforations of the ascending colon and two of the distal ileum. Histological study of the surgical specimen showed that all perforations were located at the centers of acute subserosal panniculitic foci. No vasculitis was discerned. In the previously reported three cases of WCD with intestinal perforation, perforation was solitary and seen in the small intestine. The cause of perforation was considered to be vasculitis in two cases. In the remaining one, panniculitis around the perforation was in chronic granulomatous stage. This was the first case of WCD in which acute subserosal panniculitis caused multiple ileocolonic perforations.