Objective: The objective of this study was to investigate the effects of levodopa on functional brain networks in Parkinson's disease.Methods: We acquired resting state functional magnetic resonance imaging in 30 drug-naïve participants with Parkinson's disease and 20 age-matched healthy controls. Each participant was studied following administration of a single oral dose of either levodopa or placebo in a randomized, double-blind, crossover design.Results: The greatest observed differences in functional connectivity were between Parkinson's disease versus control participants, independent of pharmacologic intervention. By contrast, the effects of levodopa were much smaller and detectable only in the Parkinson's disease group. Moreover, although levodopa administration in the Parkinson's disease group measurably improved motor performance, it did not increase the similarity of functional connectivity in Parkinson's disease to the control group.Conclusions: We found that a single, small dose of levodopa did not normalize functional connectivity in drug-naïve Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]