Objective: Mechanical characteristics of high-velocity, low-amplitude spinal manipulations (HVLA-SMs) can vary. Sustained changes in peripheral neuronal signaling due to altered load transmission to a sensory receptor's local mechanical environment are often considered a mechanism contributing to the therapeutic effects of spinal manipulation. The purpose of this study was to determine whether variation in an HVLA-SM's thrust amplitude and duration alters the neural responsiveness of lumbar muscle spindles to either vertebral movement or position. Methods: Anesthetized cats (n = 112) received L6 HVLA-SMs delivered to the spinous process. Cats were divided into 6 cohorts depending upon the peak thrust force (25%, 55%, 85% body weight) or thrust displacement (1, 2, 3 mm) they received. Cats in each cohort received 8 thrust durations (0-250 milliseconds). Afferent discharge from 112 spindles was recorded in response to ramp and hold vertebral movement before and after the manipulation. Changes in mean instantaneous frequency (Delta MIF) during the baseline period preceding the ramps (Delta MIFresting), during ramp movement (Delta MIFmovement), and with the vertebra held in the new position (Delta MIFposition) were compared. Results: Thrust duration had a small but statistically significant effect on Delta MIFresting at all 6 thrust amplitudes compared with control (0-millisecond thrust duration). The lowest amplitude thrust displacement (1 mm) increased Delta MIFresting at all thrust durations. For all the other thrust displacements and forces, the direction of change in Delta MIFresting was not consistent, and the pattern of change was not systematically related to thrust duration. Regardless of thrust force, displacement, or duration, Delta MIFmovement and Delta MIFposition were not significantly different from control. Conclusion: Relatively low-amplitude thrust displacements applied during an HVLA-SM produced sustained increases in the resting discharge of paraspinal muscle spindles regardless of the duration over which the thrust was applied. However, regardless of the HVLA-SM's thrust amplitude or duration, the responsiveness of paraspinal muscle spindles to vertebral movement and to a new vertebral position was not affected. (J Manipulative Physiol Ther 2013;36:68-77)