Injuries to the anterior cruciate ligament frequently occur under combined mechanisms of knee loading. This in vitro study was designed to measure levels of ligament force under dual combinations of individual loading states and to determine which combinations generated high force. Resultant force was recorded as the knee was extended passively from 90 degrees of flexion to 5 degrees of hyperextension under constant tibial loadings. The individual loading states were 100 N of anterior tibial force, 10 Nm of varus and valgus moment, and 10 Nm of internal and external tibial torque. Straight anterior tibial force was the most direct loading mechanisms; the mean ligament force was approximately equal to applied anterior tibial force near 30 degrees of flexion and to 150% of applied tibial force at full extension. The addition of internal tibial torque to a knee loaded by anterior tibial force produced dramatic increases of force at full extension and hyperextension. This loading combination produced the highest ligament forces recorded in the study and is the most dangerous in terms of potential injury to the ligament. In direct contrast, the addition of external tibial torque to a knee loaded by anterior tibial force decreased the force dramatically for flexed positions of the knee; at close to 90 degrees of flexion, the anterior cruciate ligament became completely unloaded. The addition of varus moment to a knee loaded by anterior tibial force increased the force in extension and hyperextension, whereas the addition of valgus moment increased the force at flexed positions. These states of combined loading also could present an increased risk for injury. Internal tibial torque is an important loading mechanism of the anterior cruciate ligament for an extended knee. The overall risk of injury to the ligament from varus or valgus moment applied in combination with internal tibial torque is similar to the risk from internal tibial torque alone. External tibial torque was a relatively unimportant mechanism for generating anterior cruciate ligament force.