BACKGROUND Transcranial magnetic stimulation (TMS) provides a method to examine cortico-cortical motor excitability and hemispheric asymmetry in unmedicated and medicated schizophrenia patients. METHODS Fourteen right-handed schizophrenia patients (seven on conventional neuroleptics and seven medication-free) were compared with seven right-handed, age- and gender-matched normal control subjects. Motor threshold for induction of motor-evoked potentials (MEPs) and bihemispheric intracortical inhibition and facilitation were measured with single-pulse and paired-pulse TMS. RESULTS Medicated patients showed an approximately 5% higher motor thresholds in both hemispheres than unmedicated patients and control subjects. Normal control subjects had a nearly 10% higher threshold for the left than the right hemisphere, whereas the opposite was true for the patient groups (5-10% higher threshold on the right than the left). Medicated patients showed significantly decreased intracortical inhibition relative to unmedicated patients and control subjects. This difference was more pronounced for the right than for the left hemisphere. CONCLUSIONS Treatment with conventional neuroleptics is associated with increased motor threshold and decreased intracortical inhibition, whereas unmedicated patients did not differ from normal control subjects on these measures; however, schizophrenia may be characterized by a reversed pattern of interhemispheric corticospinal excitability.