Background: Parkinson disease (PD) is a neuropsychiatric disease that is characterized by motor and neuropsychiatric symptoms. Multiple neurotransmitter systems, including the serotonergic system, are involved in the pathophysiology of this disease. The exact role of the serotonergic system in PD is still unclear. Objective: To investigate the role of serotonin on specific aspects of cognition, mood, and motor performance in PD. Methods: In a double-blind, randomized, placebo-controlled, crossover design, the effects of a nonspecific serotonergic challenge with citalopram, a selective serotonin reuptake inhibitor, and a 5-HT1a receptor-specific challenge with buspirone on the Visual Verbal Learning Task, Concept Shifting Task, Profile of Mood State Questionnaire, motor section of the Unified Parkinson Disease Rating Scale (section 3), Simple Reaction Time Task, and Finger Precuing Task were studied in 21 PD patients in early stages of their disease and 21 age-, sex-, and education-matched healthy volunteers. Results: The scrotonergic challenges resulted in similar effects for both groups. No changes of scores on the cognitive tasks (Visual Verbal Learning Task and Concept Shifting Task) were observed. Results of the Profile of Moods State Questionnaire indicated that, at baseline, PD patients scored less than controls on all 5 subscales. Motor performance (measured by reaction. time) was negatively affected by the interventions. Conclusions: The effects of nonspecific and 5-HT1a receptor-specific challenging of the scrotonergic neurotransmitter system had similar effects in both PD patients and healthy control subjects. These findings indicate that serotonergic function is not impaired in early PD and that scrotonin, although involved in the pathophysiology of PD, does not seem to play a direct role in cognition, mood, and motor performance in PD patients, but may be involved in hypokinesia.