Twelve Looser zones and 17 healing bands of the ribs obtained from autopsy cases of Itai-itai disease were analyzed by bone histomorphometry. Furthermore, proper cancellous tissue of the ribs from 24 autopsy cases of Itai-itai disease with Looser zones or with the healing bands, 27 autopsy cases of Itai-itai disease without such lesions, and 29 control cases were studied by the same method to pursue the histogenesis of Looser zones. In translucent zones of Looser zones, 94% of the cancellous bone was occupied by thick woven bone in which 72% was woven osteoid and 22% was woven mineralized bone. In adjacent scleroses, 71% of the cancellous bone was occupied by woven bone in which 37% was woven mineralized bone, and 34% was woven osteoid; 53% of the cancellous bone consisted of mineralized bone. As compared with those in translucent zones, woven osteoid was decreased, and mineralized bone was increased significantly in the cancellous bone of adjacent scleroses. A significant increase of lamellar mineralized bone and a decrease of woven bone in healing bands were observed as compared with those in Looser zones. These findings suggest that the healing starts from the edge of the Looser zone, and slowly proceeds toward the center. In the cancellous bone of the ribs, the volume, thickness, and surface of osteoid and woven bone were significantly increased in patients with Itai-itai disease, with Looser zones as compared with those without Looser zones. It was concluded that Looser zones seem to occur in severe osteomalacic bones that contain abundant woven bone in the patients of Itai-itai disease.