The present study tested the hypothesis that salmon cardiac peptide (sCP), a new member of the family of natriuretic peptides, has an important role in the regulation of fluid balance and cardiovascular function. Intra-arterial administration of sCP increased urine output in salmon. It had a diuretic effect in rat as well, but the potency was lower. sCP increased the sodium excretion in proportion to the increased urine flow. Blood pressure was not affected by sCP in either species. Acute volume expansion elevated the plasma level of sCP in salmon, and an acute transfer of salmon from fresh to sea water decreased the circulating sCP level. Cardiac immunoreactive sCP or sCP mRNA levels were not affected by transfer to sea water. These results indicate that sCP has an important physiological role in defending salmon against volume overload but that it does not appear to contribute to the short-term regulation of blood pressure. sCP provides an excellent model of the general mechanisms of regulation of the A-type (atrial) natriuretic peptide system.