OBJECTIVE: To simultaneously quantify vertebral motions and neuromuscular and spinal nerve root responses to mechanical force, manually assisted, short-lever spinal manipulative thrusts. METHODS: Four patients underwent lumbar laminarthrectomy to decompress the central spinal canal and neuroforamina, as clinically indicated. Prior to decompression, finely threaded, 1.8-mm diameter intraosseous pins were rigidly fixed to the lumbar spinous process (L1 or L3) using fluoroscopic guidance, and a high-frequency, low-noise, 10-g, triaxial accelerometer was mounted to the pin. Following decompression, 4 needle electromyographic (nEMG) electrodes were inserted into the multifidus musculature adjacent to the pin mount bilaterally, and 2 bipolar platinum electrodes were cradled around the left and right S1 spinal nerve roots. With the spine exposed, spinal manipulative thrusts were delivered internally to the lumbosacral spinous processes and facet joints and externally by contacting the skin overlying the respective spinal landmarks using 2 force settings ( approximately 30 N, < 5 milliseconds (ms); approximately 150 N, < 5 ms) and 2 force vectors (posteroanterior and superior; posteroanterior and inferior). RESULTS: Spinal manipulative thrusts resulted in positive electromyographic (EMG) and compound action potential (CAP) responses that were typically characterized by a single voltage potential change lasting several milliseconds in duration. However, multiple EMG and CAP discharges were observed in numerous cases. The temporal relationship between the initiation of the mechanical thrust and the neurophysiologic response to internal and external spinal manipulative therapy (SMT) thrusts ranged from 2.4 to 18.1 ms and 2.4 to 28.6 ms for EMG and CAP responses, respectively. Neurophysiologic responses varied substantially between patients. CONCLUSIONS: Vertebral motions and resulting spinal nerve root and neuromuscular reflex responses appear to be temporally related to the applied force during SMT. These findings suggest that intersegmental motions produced by spinal manipulation may play a prominent role in eliciting physiologic responses.