OBJECTIVE: Musculoskeletal conditions of the knee involve changes in sensorimotor function, but it is unclear whether these changes are a cause or result of pain. Induction of experimental pain may help solve this issue. Although this is commonly achieved by injection of hypertonic saline into muscle, muscle is commonly not the source of pain. This study investigated whether pain induced by injection of saline into the infrapatellar fat pad changes motor control of the quadriceps muscles of the knee. METHODS: Ten participants performed a standardized task involving ascending and descending a series of steps. Electromyographic activity (EMG) of vastus medialis obliquus (VMO) and vastus lateralis (VL) was recorded with surface electrodes. Trials were conducted without pain, with anterior knee pain induced by injection (0.25 ml) of hypertonic saline (5%) into the infrapatellar fat pad, with anticipation of pain associated with unpredictable electrical shocks to the knee, and 20 minutes after pain cessation. EMG onset and amplitude were analyzed. RESULTS: When participants ascended the steps with pain, the onset of VMO EMG was delayed relative to that of VL, in contrast to simultaneous or earlier activation of VMO EMG in the pre- and postpain trials. VL EMG amplitude was decreased significantly from the control condition. CONCLUSION: These data show that alterations in coordination of knee muscle activity can be caused by pain, even when it is of nonmuscle origin. Treatment of pain is therefore important to facilitate performance of the quadriceps muscles, which are essential for locomotor and functional tasks as well as for knee stability.