Even though levodopa can provide effective therapy for symptomatic relief of parkinsonism, many patients deteriorate over time. This change may be related to a loss of storage capability for dopamine in the brain affected by parkinsonian changes. Some of the variability in drug action is determined by its peripheral pharmacokinetics. Methods that can enhance dose-by-dose effectiveness, including controlled-release preparations and enteral infusions, have practical applications for managing "wearing-off" or peak-effect problems.