We tested the principle of guided tissue regeneration (GTR) for healing segmental long-bone defects. 7 mm (3 animals) or 10 mm (5 animals) long segmental defects were created in the diaphyses of both radii in 8 rabbits. The defect on one side was covered with a barrier membrane of expanded polytetrafluoroethylene membrane shaped as a tube, while the contralateral side with no membrane served as the control. Healing was followed with radiographs obtained repeatedly during a 13- (n 3) or 27- (n 5) week period. Thereafter, the animals were killed and ground sections of the defect sites were prepared for histologic examination. Radiographically, the control sites showed some early subperiosteal callus formation and nonunion of the defects after 6 weeks. The bone ends were rounded off and sealed with cortical bone. No major changes were noted after 6 weeks. At the test sites, subperiosteal bone formation at the bone ends was first observed radiographically at 2 weeks. At 9 weeks, a thin cortical bone bridged the defect along the inner surface of the membrane. Histologically, an interrupted line of thin, cortical bone was observed along the inner surface of the barrier membrane. Fatty bone marrow occupied the central and largest volume of the defect. We conclude that it seems possible to use the principle of GTR to accomplish bone union of segmental long-bone defects.