In two 4-week polysomnography pilot studies with 10 patients each, we investigated the efficacy of oral lisuride as monotherapy in de novo RLS patients as well as in combination with levodopa in advanced RLS. Daily doses at study end were 0.3 mg lisuride, plus 150 mg levodopa in the combination study. Marked improvements occurred in both studies in different PLM indexes and in the CGI. Levodopa dose could be decreased by 27%. Lisuride might be an efficacious treatment for RLS in general, and in combination with levodopa in advanced stage.