The renal response to iso-oncotic blood volume expansion with bovine serum albumin was studied in anaesthetized homozygous Brattleboro (DI) rats after acute (1 day) pretreatment with 1 U arginine-vasopressin (AVP) compared to heterozygous controls. In AVP-treated DI (DI+AVP) rats, basal urine flow as well as urinary sodium, chloride, and potassium excretion, were not different from controls. Diuresis and kaliuresis induced by volume expansion were blunted in DI+AVP rats. However, natriuresis and chloruresis were exaggerated in DI+AVP rats. They increased faster, reached a higher maximum, but declined earlier, compared to controls. The blunted diuresis resulted in a positive volume balance by the end of the experiment in DI+AVP rats, whereas the controls showed restoration of normal balance. Significant retention of sodium and chloride was observed in controls, but not in DI+AVP rats, over the time of the experiment. DI+AVP rats lost significantly less potassium than controls during the experiment. As judged from the lithium clearance method, the exaggerated saluresis in DI+ AVP rats was mainly due to a reduced proximal sodium reabsorption. Plasma immunoreactivity of atrial natriuretic peptide (ANP) rose during blood volume expansion and fell in the recovery period. It was not different between AVP-treated DI rats and controls at any time of the experiment. Inulin clearance was slightly, but not significantly, lower in DI+AVP rats and increased after blood volume expansion in DI+AVP rats only. The results indicate that acute AVP substitution may abolish the exaggerated volume loss, but not the increased saluresis known to occur in DI rats after blood volume expansion.