Extracellular dopamine (DA) concentrations estimated by transcerebral dialysis and D1-dependent c-fos expression, as demonstrated by Fos immunohistochemistry, were studied after blockade of DA reuptake by GBR-12909. Rats implanted with dialysis probes in the dorsal caudate-putamen did not show any Fos-positive neuronal labeling in the implanted area or in the rest of the caudate-putamen. Administration of GBR-12909 dose-dependently increased DA output in dialysates and resulted in the appearance in the caudate-putamen of Fos-positive neurons whose density was related to the dose of GBR- 12909 and to the increase in extracellular concentrations of DA. The D1 antagonist SCH-23390 blocked GBR-12909-induced activation of Fos while potentiating the stimulation of DA output. The results show that following blockade of DA reuptake by GBR-12909, the induction of Fos is related to stimulation of D1 receptors by extracellular DA. Combination of brain dialysis with Fos immunohistochemistry might provide a method for estimating the functional significance of extracellular DA as measured by brain microdialysis.