Ten patients with Parkinson's disease suffering severe motor fluctuations completed a double-blind, placebo-controlled, crossover trial of duodenal infusion of levodopa/carbidopa to determine if this technique improved the duration of functional time by reducing plasma levodopa level variability. With infusion, seven patients experienced increased functional "on" hours and decreased number of "off" episodes; however, two patients were slightly worse and one patient experienced no benefit. All 10 patients had significantly decreased variability in levodopa levels permitting better titration of levodopa dosage to individual requirements. Five patients continued to use infusion 12 to 20 months after completion of this study. Selected patients with Parkinson's disease who experience severe motor fluctuations may benefit from duodenal infusion with an improved and prolonged response to medication.