The purpose of the present study was to follow the development of periapical lesions both radiographically and histologically in infected teeth with open and sealed root canals. The mandibular premolars from five adult monkeys were used in the experiment. Sealed infected teeth developed radiographic signs of periapical pathosis significantly earlier than unsealed teeth. Although, histological signs of pathology could be seen periapically at earlier observation periods, sealed teeth consistently developed these changes earlier than unsealed teeth. Furthermore, the histological periapical pathology differed somewhat between the two groups in that unsealed teeth showed a multi-focal diffuse pattern of spreading.