OBJECTIVE—To study the diagnostic usefulness of transcallosal inhibition (TI) elicited by transcranial magnetic stimulation (TMS) in detecting central conduction deficits in early multiple sclerosis. Corticospinally mediated excitatory responses evoked by TMS are accepted as a sensitive diagnostic tool in multiple sclerosis. Recently, TI evoked by TMS has been introduced as a new paradigm to test the function of callosal fibres interconnecting both hand associated motor cortices. METHODS—Focal TMS of the motor cortex was performed in 50 patients with early relapsing-remitting multiple sclerosis. Corticospinally mediated (central motor latencies, amplitudes) and transcallosally mediated (onset latency and duration of TI) stimulation effects were investigated. RESULTS—TMS disclosed abnormalities of corticospinally mediated responses in 62% and of TI in 80% of the patients. CONCLUSION—The assessment of TI allows the discovery of lesions within the periventricular white matter that were not accessible by neurophysiological techniques before. This new paradigm increases thesensitivity of TMS with which to detect central conduction deficits inearly multiple sclerosis.