Objective: To study the transcallosal dysfunction in terms of cognitive impairment, disturbance of transcallosal motor inhibition (TCI) and morphological involvement in patients with mild multiple sclerosis (MS). Methods: Thirty-five MS patients with mean EDSS of 2,5 and 30 control subjects were submitted to a neuropsychological test battery testing including attention, language and memory as well as tasks that predominantly assess interhemispheric functions. The transcallosal inhibition was assessed by transcortical magnetic stimulation and lesion loading in MS patients was assessed by T2 weighted and FLAIR magnet resonance imaging (MRI). Results: Patients had only discrete impairment of transcallosal motor inhibition but showed a significantly impaired performance of neuropsychological tasks, especially of those including transcallosal pathways. While the results of neuropsychological examination were highly correlated with EDSS and periventricular lesion load, the TCI showed no relationship. Conclusion: The present data suggest, that (1) periventricular and callosal lesions are reflected by dysfunction of transcallosal interhemispheric pathways and (2) appropriate neuropsychological testing is more capable to detect this transcallosal dysfunction in early states of multiple sclerosis than electrophysiological tests of transcallosal motor inhibition.