Objective: The corpus callosum (CC) is commonly affected in multiple sclerosis (MS). The ipsilateral silent period (iSP) is a putative electrophysiological marker of callosal demyelination. The purpose of this study was to re-assess, under recently established optimised protocol conditions [Jung P., Ziemann U. Differences of the ipsilateral silent period in small hand muscles. Muscle Nerve in press.], its diagnostic sensitivity in MS, about which conflicting results were reported in previous studies. Methods: ISP measurements (onset, duration, and depth) were obtained in the abductor pollicis brevis (APB) muscle of either hand in 49 patients with early relapsing-remitting MS (RRMS) (mean EDSS, 1.3). Standard central motor conduction times to the APB (CMCTAPB) and tibial anterior muscles (CMCTTA), and magnetic resonance images (MRI) were also obtained. Results: ISP measurements showed a similar diagnostic sensitivity (28.6%) as CMCTAPB (24.5%), while diagnostic sensitivities of CMCTTA (69.4%) and MRI of the CC (78.6%) were much higher. Prolongation of iSP duration was the most sensitive single iSP measure. ISP prolongation occurred more frequently when CMCTAPB to the same hand was also prolonged (40.0% vs. 8.4%, p < 0.000 1). The correlation between iSP duration and CMCTAPB was significant (Pearson's r=0.24, p < 0.02), suggesting that iSP duration can be contaminated by demyclination of the contralateral corticospinal tract. ISP duration did not correlate with MRI abnon-nalities of the CC. Conclusions: ISP measures are neither a sensitive nor a specific marker of callosal conduction abnormality in early RRMS. (c) 2006 Elsevier B.V. All rights reserved.