Urodilatin, a renal natriuretic peptide that is an analogue to circulating atrial natriuretic peptide [alpha-ANP(99-126)], is measurable with a highly specific and sensitive radioimmunoassay. While most ANP antibodies cannot distinguish between urodilatin and other ANP analogues, the polyclonal urodilatin antibody specifically measures human urodilatin without any cross-reactivity to other ANP analogues. Urodilatin is not detected in blood from healthy volunteers nor from cardiac patients. Urinary urodilatin accounts for only a part of total urinary ANP immunoreactivity. Urodilatin excretion closely parallels sodium excretion in response to an acute volume load while changes in urinary immunoreactive ANP excretion do not reflect this renal response. We conclude that specific urodilatin assays are required to explore further the physiological role of the renal natriuretic peptide.