The long-duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.