1. DARPP-32 is a phosphoprotein regulated by dopamine and cAMP. In its phosphorylated form it acts as an inhibitor of protein phosphatase-1, thereby regulating the phosphorylation state of phosphoproteins in the basal ganglia. 2. In the kidney, DARPP-32 has been detected in the medullary thick ascending limb of Henle (mTAL) and, to a lesser degree, in the proximal convoluted tubule by means of immunohistochemistry and in situ hybridization. 3. In single microdissected tubules of rat kidney, Na+, K(+)-ATPase activity, measured as ouabain-sensitive ATP hydrolysis, has been shown to be inhibited to the same degree by the DA1 agonist fenoldopam, cAMP and a synthesized and phosphorylated DARPP-32 peptide, D32(8-38). 4. It is concluded that the DA1 receptor-mediated inhibition of Na+ transport in the mTAL by dopamine occurs via cAMP accumulation and the phosphoprotein, DARPP-32.