It has been suggested that sleep disturbances in multiple sclerosis (MS) may be related to periodic leg movements (PLM) during sleep, but to date polysomnographic studies were conducted only on small and unselected patient groups. Aim of this study was to evaluate 8-hour polysomnography in MS patients and to correlate sleep results with clinical and brain magnetic resonance imaging (MRI) data. Twenty-five clinically definite MS patients, without mood disorders and drug-free, entered the study. The patients were compared to 25 age- and sex-matched subjects. MS patients had significantly reduced sleep efficiency and experienced more awakenings during sleep. No difference was found in sleep architecture parameters between MS patients and controls. PLM was found in 9 patients (36%) and 2 controls (8%; p = 0.02). Of the six patients who complained of insomnia two had PLM and 2 others presented with PLM and central sleep apnea. In patients with PLM greater MRI lesion loads were detected in the infratentorial regions, particularly in cerebellum and brainstem. Larger studies in neurological diseases that produce focal lesions in these brain areas could provide useful information on the PLM pathogenesis.