Summary.This study was conducted to: (i) establish a monkey model system for studying the healing of root perforations, (ii) follow and define the normal healing processes of peiodontal tissues after root perforation and attempted repair, and (iii) assess the nature of periodontal tissue responses to a hard‐set calcium hydroxide treatment of experimental root perforations under aseptic conditions. Forty‐eight teeth of two rhesus monkeys were used. Twenty‐four root perforations were treated with a hard‐setting calcium hydroxide compound, while 24, sealed with teflon dises, served as controls. Observation periods were 2, 4, 7, 14, 21 and 42 days; radiographic and histological observations were conducted on each tooth. After the animals were killed, the tissues were demineralized and prepared for histological examination. Radiographs were taken at the time of perforation and again at the time of sacrifice.Following radiological and histological analysis, a number of observations were made. In both treatment and control groups, the teeth with lateral and furcal perforations presented the same sequence of tissue responses with time. Tissue responses at the wound sites and within the perforation canals were classified into three phases. The initial phase was characterized by blood clot formation, pronounced polymorphonuclear leucocyte infiltration, and incipient necrosis within the periodontal ligament coronal to the lateral lesions. The intermediate phase was characterized by resolution of the blood clot, granulation tissue formation, and resorption of necrotic debris, bone, cementum and dentine fragments. The late phase was characterized by resolution of the inflammation, maturation of the connective tissue, bone tissue healing with proliferation of trabecular bone into the perforation canal, reparative cementum formation along the cut dentinal wall in the perforation canal, and ankylosis in lateral lesions. Only four out of the 48 lesions developed bacterial contamination and abscess formation at the woun