This study was performed to demonstrate global and regional cerebral blood flow (rCBF) changes during rapid eye movement (REM) sleep in six patients with narcolepsy using SPECT and 99mTc-HMPAO. METHODS Global and hemispheric HMPAO uptake as well as regional (RI) and asymmetry indices were estimated and compared between polysomnographically verified sleep onset (SO)REM and wakefulness. RESULTS The estimated global HMPAO uptake did not differ between the two conditions indicating a similar overall cortical activity. During (SO)REM sleep, hemispheric HMPAO uptake as well as calculated RI, especially in the supratemporal plane, were significantly higher on the right side than contralateral. This indicates an initially right-sided cerebral activation and a special involvement of the right, nondominant hemisphere during dreaming which is responsible for visual-spatial perceptions. Furthermore, increased RI in superior parietal regions during sleep were evident and were explained by an activation of associative areas. In thalamic regions, decreased RI were found during sleep, which may reflect thalamic dysfunction. CONCLUSIONS A definite assignment of these CBF alterations to (SO)REM sleep might be problematic because of unstable boundaries between sleep stages in narcolepsy. On the other hand, specificity of such CBF changes for narcolepsy requires further study.