We evaluated brainstem dysfunction in a girl with Leigh disease. Neuroradiological and neurophysiological tests included brain magnetic resonance imaging, [123I]IMP single-photon emission computed tomography (SPECT), auditory brainstem responses (ABRs), short-latency somatosensory evoked potentials (SSEPs), electrically elicited blink reflexes (BRs) and all night polysomnography (PSG). The basal ganglia and midbrain contained areas of low accumulation on [123I]IMP SPECT images. Serial analysis of ABRs and SSEPs showed progressive disturbances of the brainstem wave components. The R2 components of the BRs were impaired. All night PSG revealed disturbances in both the tonic and phasic components of REM sleep. These findings suggested the multimodality tests in combination with neuroradiologic examinations are useful for assessing brainstem dysfunction in patients with Leigh disease.