The different murine D2-type dopamine receptors (D2L, D2S, D3L, D3S, and D4) were expressed in Xenopus laevis oocytes. The D2-type receptors were all similarly and efficiently expressed in Xenopus oocytes and were shown to bind the D2 antagonist [125I]sulpride. They were all shown to activate Cl- influx upon agonist stimulation. Using the diagnostic inhibitor bumetanide, we were able to separate the Na+/K+/2Cl- cotransporter component of the Cl- influx from the total unidirectional Cl- influx. The D3L subtype was found to operate exclusively through the bumetanide-insensitive Cl- influx whereas the other D2-type receptors acted on the Na+/K+/2Cl- cotransporter as well. The pertussis toxin sensitivity of the receptor-activated chloride influx via the Na+/K+/2Cl- cotransporter varied between the various D2-type receptors showing that they may couple to different G proteins, and activate different second messenger systems.