We evaluated whether patients with early-onset Parkinson's disease (EOPD) have a different clinical profile and pharmacological response than those with late-onset disease (LOPD). We performed a retrospective analysis and an acute pharmacological challenge with L-Dopa in 34 EOPD (age at onset between 21 and 40 years) and 34 LOPD (onset after age 60) patients. All patients completed a structured questionnaire cross-checked against medical record charts and underwent an acute levodopa test. Most significant differences were in the mode of onset, time of diagnosis, and degree of initial improvement. We did not observe differences with regard to motor fluctuations. The acute levodopa test showed no differences in latency to response onset between groups. However, the magnitude of the response was greater and the duration shorter in EOPD patients. Younger patients had greater reductions in bradykinesia scores, whereas posture/gait symptomatology was less responsive in older patients. The type and severity of dyskinesias also differed significantly between groups. Our findings suggest that central pharmacokinetics, pharmacodynamics, and possibly, nondopaminergic systems play a role in the age-related differences observed in Parkinson's disease.