The temporal response of microdialysis probes in vivo was followed with 1-min sampling. The response under four conditions was examined: in vitro sampling of dopamine (DA), in vitro perfusion of DA, in vivo perfusion of DA, and in vivo perfusion of cocaine. The temporal response of the probe in a stirred solution at 37 degrees C for both sampling mode and perfusion mode was determined using a flow rate of 1.6 microL/min. As expected, the rate of gain or loss of DA in these two cases rapidly stabilized. The in vivo response to a step change in perfusate concentration was also examined. The rate of loss of DA into the tissue rapidly reached a steady state so that the dialysate DA concentration stabilized within 2 min. To examine the in vivo response of DA to a step change in drug concentration, dialysis probes in the striata of anesthetized rats were perfused with artificial cerebrospinal fluid interchanged with 20 microM cocaine. The increase in DA caused by its uptake inhibition by cocaine rapidly reached a maximum level in 2-4 min and then gradually decreased. After the cocaine was removed, the dialysate concentration of DA fell rapidly with some tailing, suggesting the presence of residual cocaine in the tissue. These results suggest that relatively fast changes in DA levels in tissue can be followed by microdialysis probes. The rapid stabilization also suggests that the DA concentration profile does not extend very far from the probe.