The aim of the present study was to determine whether dopamine affects NaCl reabsorption in the medullary thick ascending limb of the loop of Henle. Basolateral dopamine (10(-6) M) significantly inhibited Cl- reabsorption in the in vitro microperfused rat medullary thick ascending limb by 21 +/- 2% (P < 0.01). The response to 10(-6) M dopamine was completely blocked by pretreatment with the dopamine D1 receptor antagonist R(+)-SCH-23390 (5 x 10(-5) M), and was mimicked by the dopamine D1 receptor agonist A-77636 (10(-6) M; delta - 36 +/- 2%; P < 0.05). In contrast, basolateral administration of the dopamine D2 receptor agonist (+)-bromocriptine (10(-6) M) transiently increased Cl- reabsorption by 49 +/- 18% (P < 0.05). Neither the D1 nor the D2 agonist affected Cl- reabsorption when selectively administered to the luminal membrane. These data suggest that the predominant effect of dopamine on the medullary thick ascending limb of the rat is to inhibit the reabsorption of NaCl, a response which is mediated by dopamine D1 receptors.