<i>Background:</i> Renal dopamine exerts natriuretic and diuretic effects by activating D₁-like receptors. Uninephrectomy results in increased renal dopaminergic activity and dopamine-sensitive enhanced natriuresis. <i>Methods:</i> The present study evaluated renal adaptations in sodium handling and the role of dopamine in rats submitted to ¾ nephrectomy: right nephrectomy and excision of both poles of the left kidney (¾nx rats). <i>Results:</i> Two weeks after surgery the absolute urinary levels of dopamine were markedly reduced in ¾nx rats whereas the urinary dopamine excretion per % of residual nephrons was significantly increased in the remnant kidney of ¾nx rats. The V_max values for renal aromatic <i>L</i>-amino acid decarboxylase, the enzyme responsible for the synthesis of renal dopamine, were decreased in ¾nx rats. Renal catechol-<i>O</i>-methyltransferase activity, the enzyme responsible for the methylation of dopamine, was increased in ¾nx rats whereas the renal activities of monoamine oxidases A and B did not differ between ¾nx and Sham animals. Volume expansion (5% body weight) resulted in similar natriuretic responses in ¾nx and Sham rats. During D₁ antagonist administration (Sch-23390, 30 µg·h^–1·kg^–1) the natriuretic response to volume expansion was reduced in ¾nx rats more pronouncedly than in Sham animals. <i>Conclusion:</i> The decrease in absolute renal dopamine output in ¾nx rats is related with reduced renal synthesis and enhanced <i>O</i>-methylation of the amine. However, this is accompanied in ¾nx rats by increased renal dopamine excretion per residual nephrons and dopamine-sensitive enhanced natriuresis.