The purpose of this study was to identify the changes in the force-frequency relationship (FFR) of the human quadriceps femoris muscle following electrically and voluntarily induced fatigue. Twenty nondisabled subjects each participated in one experimental session to test the effects of electrically induced fatigue on the FFR; 10 of these subjects participated in a second session in which voluntarily induced fatigue was produced. Fatigue was induced by having subjects perform repeated, 8-second, isometric contractions followed by 12-second rests until 50% of the initial force was produced. Markedly decreased forces were seen at all frequencies tested following fatigue. Low frequency fatigue was observed following both fatiguing protocols. The frequencies needed to produce near-maximum forces did not shift with fatigue. These results suggest that the most appropriate stimulation frequency to use when activating skeletal muscle depends on both the percentage of tetanic force desired and the fatigue state of the muscle. This study also provides the clinician with data on the FFR of healthy human quadriceps femoris muscle prior to fatigue. [Binder-Macleod SA, McDermond LR. Changes in the force-frequency relationship of the human quadriceps femoris muscle following electrically and voluntarily induced fatigue.