The purpose of this investigation was to study in unanesthetized rats the blood pressure, renal and hematocrit responses to dextronatrin, a structural analogue of atrial natriuretic peptides (ANP). The peptide was infused intravenously for 20 min at doses of either 1 or 20 micrograms/min in binephrectomized rats as well as in rats with intact kidneys. The experiments were started 2 h after preparation of the rats under ether anesthesia. In binephrectomized rats, the small dose of dextronatrin lowered blood pressure and raised hematocrit. In those rats, the larger dose of the investigational peptide had no blood pressure lowering effect, but still increased hematocrit. Dextronatrin had no effect on heart rate, both in rats with and without kidneys. Dextronatrin given at the 1 microgram/min dose to normal rats caused a significant increase in urinary Na excretion. The large dose, however, did not modify this parameter. The effect of dextronatrin (1 microgram/min for 20 min) on splanchnic nerve activity was evaluated in other normal rats after a recovery period of 24 h from surgical procedure. Integrated nerve activity was found to significantly increase in parallel with heart rate while blood pressure was reduced. Taken together, these results show that a low dose of dextronatrin lowers blood pressure and induces an increase in urinary Na excretion and hematocrit. They also indicate that the blood pressure and renal effects of the peptide are abolished when a high dose is administered. In addition, it appears that the shift of fluid from the intra- to the extravascular compartment, reflected in binephrectomized rats by an increase in hematocrit, does not depend on the level of systemic blood pressure. Finally, the present observations suggest that the blood pressure lowering effect of dextronatrin is accompanied in the conscious rat by a stimulation of the sympathetic nervous system.