Levodopa has been the mainstay treatment for Parkinson's disease for several decades, but the precise mechanism for its therapeutic action is still not well understood. To date, little distinction has been made between the effects of levodopa on the different brain DA pools. We studied the levodopa action on two extracellular DA pools: one was analyzed by microdialysis (often considered as indicative of volume transmission) and the other by in vivo amperometry during nigrostriatal cell stimulation (more indicative of neurotransmission). Levodopa administration induced a moderate (↓200%) and tardy (began at 60 min) increase in the DA-pool measured by microdialysis, an effect that increased (↓500%) and accelerated (began at 10 min) after DA-cell degeneration. Levodopa action on the DA-pool measured by amperometry was very fast (10 min) and prominent (↓600%) in normal rats. The DA-denervated striatum showed a fast exhaustion during cell stimulation, which prevented further study of the levodopa effect on the DA amperometry-pool under this condition. This study suggests a different kinetic for levodopa action on the volume transmitter and neurotransmitter DA-pool, showing marked changes in levodopa action in the denervated striatum.