The objective of this study was to determine the cause of median forearm motor conduction velocity (FMCV) slowing in patients with carpal tunnel syndrome, due to either focal conduction abnormality over wrist or retrograde conduction slowing, and to decide whether the slowing is related to severity of compression or not. Fifty carpal tunnel syndrome patients confirmed by conventional nerve conduction study with abnormal electromyography of the abductor pollicis brevis muscle were group 1, and 100 with normal electromyography, group 2. One hundred volunteers served as controls. In addition to conventional nerve conduction study of median and ulnar nerves, palmar stimulations for median mixed and motor nerves were also performed to calculate wrist-palm mixed nerve conduction time and motor conduction velocity (W-P MCV). For group 1, group 2, and control subjects, respectively, W-P MCV were 19.73+/-7.65 (mean+/-SD), 32.7+/-6.83, and 52.75+/-6.4 m/s, whereas median FMCV were 48.63+/-8.32, 54.42+/-2.11, and 57.86+/-4.24 m/s. There was a significant reduction in the W-P MCV (62.6%, P<0.00001) and a decrease in the median FMCV (15.95%, P<0.00001) in group 1, and 38% reduction in W-P MCV (P<0.00001) and 5.9% decrease in median FMCV (P<0.00001) in group 2 when compared with controls, but ulnar FMCV and sensory nerve conduction study results did not, suggesting the reduction of median W-P MCV is not parallel with that of median FMCV in both patients groups. Furthermore, there is a poor correlation of median FMCV and W-P MCV in patient groups, implying conduction blockage of the large myelinating fibers at the wrist, leaving only slower axons to be measured, is not the likely cause of reduction of FMCV. In addition, the reduction of compound muscle action potential amplitude of abductor pollicis brevis muscle, conduction block at wrist and weak correlation of median FMCV and compound muscle action potential amplitude of abductor pollicis brevis exclusively occurred in group 1. Therefore, the retrograde conduction slowing really occurs among patients with carpal tunnel syndrome-markedly in those with abnormal electromyography and mildly in those with only demyelination. This finding counters conventional wisdom that nerve function changes only in segments distal to injured sites.