Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. Methods: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. Results: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Conclusions: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament—i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic ga
