Study Design An in vitro biomechanical investigation using human lumbar cadaveric spine specimens was undertaken to determine any relationship between intervertebral disc degeneration and nonlinear multidirectional spinal flexibility. Summary of Background Data Previous clinical and biomechanical studies have not established conclusively such a relationship. Methods Forty-seven discs from 12 whole lumbar spina specimens were studied under the application of flexion-extension, axial rotation, and lateral bending pure moments. Three flexihility parameters were defined (neutral zone (NZ), range of motion (ROM), and neutral zone ratio (NZR = NZROM)) and correlated with the macroscopic and radiographic degeneration. Results and Conclusions In flexion-extension, the ROM decreased and NZR increased with degeneration. In axial rotation, NZ and NZR increased with degeneration. In lateral binding, the ROM significantly decreased and the NZR increased with degeneration. In all three loading directions, the NZR increased, indicating greater joint laxity with degeneration.