Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 pmol . kg(-1).min(-1)) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively), Mean arterial blood pressure did not change with any infusion of 6 or 20 mu mol.kg(-1).min(-1). During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14 +/- 2 to 7 +/- 2 pg/ml and sodium excretion increased markedly(2.3 +/- 0.8 to 19 +/- 8 mu mol/min), whereas glomerular filtration rate (GFR) remained constant. IsoLoad-20 decreased plasma ANG II similarly (13 +/- 3 to 7 +/- 1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9 +/- 1.0 to 11 +/- 6 mu mol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mmHg and decreased plasma ANG II to similar to 6 pg/ml, whereas sodium excretion increased to similar to 60 mu mol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry.