In Brief Study Design. An intact bovine caudal disc model was used to investigate how combinations of biomechanical parameters influence the severity of disruption during compressive loading. Objectives. To quantify the combined influence of flex-ion, hydration level, and compressive loading rate on nuclear disruption. Summary of Background Data. The risk of disc pro-lapse is known to increase when the disc is loaded flexed. However, there are few experimental data available quantifying the extent to which loading parameters might interact to produce disruption in the healthy disc. Methods. Reproducible states of full and partial hydration were established for 96 isolated caudal discs. These discs were then subjected to compression under combined conditions of high or low hydration, zero or full flexion, and moderate or low loading rate. The extent of disc disruption was assessed macroscopically using a damage weighting procedure. Results. Maximum disruption of the intact, healthy disc occurred under combined conditions of full hydration and flexion. Loading rate, whether at 0.004 MPa/sec or 4 MPa/sec, had little influence when applied without flexion, but there was an increased risk of disruption when the moderate rate was combined with full flexion. Conclusions. The investigation demonstrates that sig-nificant levels of disruption can be induced by mechanical loading in intact discs free of degenerative change. Our findings support the hypothesis that mechanical injury to a healthy disc might initiate a process of degeneration. Intact bovine discs were subjected to a combined parameter biomechanical investigation involving zero and full flexion, high and low hydration, and moderate and low rates of loading. Significant levels of disruption were shown to be induced mechanically in the intact disc, suggesting that injury may initiate the degenerative cascade.