Previously, we developed technology that coupled high-speed chronoamperometry with microejections of dopamine (DA) to measure DA clearance in the brains of freely-behaving rats. Here, by varying the ejection volumes of DA across a 200-fold difference, the kinetics of striatal clearance were analyzed as a function of time and DA volume from 289 chronoamperometric signals ( n=20 rats). Each DA clearance trace was fitted to a first-order exponential decay function to determine the rate constant for DA clearance ( k). Additionally, the apparent Michaelis–Menten V max and K m kinetic constants were determined in freely-moving rats, enabling quantitative comparison of our values with other models of reuptake. The first-order rate constant for DA clearance, which reflects the V max/ K m ratio or clearance efficiency, did not vary significantly when small volumes of DA were ejected resulting in peak DA signal amplitudes ( A max) of <5 μM. However, following nomifensine-induced DAT inhibition, A max was increased and k was attenuated simultaneously with behavioral activation; and A max and behavior remained elevated beyond the initial period. Our results indicate that the analysis of kinetic parameters from chronoamperometric DA signals may be useful for investigating drug-induced regulation of DAT kinetics in relation to the behavior of freely-moving rats.