Background: Parkinson's disease (PD) is a neuropsychiatric disease, which is not only characterized by motor symptoms, but also by cognitive and psychiatric symptoms. It is hypothesized that some of the non-motor symptoms are related to the serotonergic deficiency that is present in PD. Aim: To study the influence of serotonin on cognition, memory and motor performance in PD. Methods: In a double blind, randomized, placebo-controlled, cross-over design, the effect of acute tryptophan depletion (ATD) on the Visual Verbal Learning Task (VVLT), the Concept Shifting Task (CST), Simple Reaction Time Task (SRT), Finger Precuing Task (FPT) and the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS, Section 3) was investigated in 15 PD patients in early stages of their disease and 15 healthy volunteers, matched for age, sex and educational status. Results: With the exception of the absence of a differential effect for PD patients with the long interval of the SRT, ATD produced similar effects in PD patients and control subjects on all tasks. These included impairment of delayed recall and delayed recognition on the VVLT, and improved SRT and FPT for 'short intervals'. The UPDRS in patients remained unaffected after ATD. Conclusion: Serotonin does not appear to play a disease-specific role in cognition and reaction time in early stage PD patients, nor does acute reduction of cerebral serotonin levels affect motor symptoms in a clinically relevant way.