Plasma immunoreactive vasopressin (iAVP) was studied by RIA in a patient suffering from polyuria during chronic treatment with lithium. The combined use of two antisera specific for different regions of the AVP molecule allowed us to detect circulating forms which are modified in the acyclic tripeptide portion. In this lithium-treated patient, iAVP was abnormally low with respect to plasma osmolality. However, iAVP increased during hypertonic saline infusion, probably through an osmosensitive mechanism. A remarkable finding was that contrary to the observations made in healthy subjects and in another patient with diabetes insipidus, iAVP measured with the antiserum specific for the acyclic portion of the AVP molecule was below the values measured with the antiserum specific for the hexapeptide ring. This unusual immunoreactivity profile suggests that the plasma of this polyuric lithium-treated patient contains vasopressin-like peptides which differ from arginine vasopressin in the structure of the C-terminal tripeptide tail.