To clarify the role of brain ouabain-like compound in reduced renal mass-saline hypertension, we examined the effects of intracerebroventricular infusion of the Fab fragments of antidigoxin antibody (Digibind) on the change in blood pressure of saline-drinking subtotally nephrectomized rats. Twenty male Wistar rats weighing 250 g each underwent subtotal nephrectomy. Two groups of 10 rats received intracerebroventricular infusion of Digibind (20 mg/ml) or normal sheep IgG (20 mg/ml) at a rate of 0.5 microliters/h for 11 days. All rats began to drink 1% NaCl solution after two days of infusion. Systolic blood pressure was measured by the tail-cuff method on days 2, 6 and 9 of infusion. Two groups of saline-drinking rats with reduced renal mass developed hypertension. However, systolic blood pressure was significantly higher in Digibind-infused rats than in IgG-infused rats (day 2, 144 +/- 3(SEM) vs. 133 +/- 1 mmHg, p < 0.05; day 6, 161 +/- 4 vs. 151 +/- 2 mmHg, 0.05 < p < 0.1, day 9, 181 +/- 8 vs. 155 +/- 2 mmHg, p < 0.05). In spite of similar renal dysfunction, plasma aldosterone concentrations, and plasma OLC levels, the accelerated increase in blood pressure was accompanied by a significantly impaired pressure-natriuresis relationship (0.089 +/- 0.013 vs. 0.131 +/- 0.013 mmol/day/mmHg, p < 0.05). These results indicate that chronic intracerebroventricular infusion of Digibind augmented reduced renal mass-saline hypertension in rats and suggest that brain ouabain-like compound may play a protective role against the elevation of blood pressure, at least in this model of hypertension.