Antibovine neurophysin antibodies (anti-bNpI and/or anti-bNpII) are present in certain patients with familial central diabetes insipidus; these are exogenous origin, as they are not present in patients who have not received treatment with crude posterior pituitary extracts over the years preceding the analysis. Immunoreactive neurophysins were detectable in the blood of five patients with familial central diabetes insipidus, and in two of them, the levels increased after a short period of water restriction. There is marked polymorphism of these neurophysins from one serum to another: neurophysin I was consistently absent, while neurophysin II, accessory neurophysins, and other immunoreactive substances not present in normal sera were sometimes present in variable amounts. Immunoreactive AVP was undetectable in the urine of all patients, while immunoreactive OT was found in three of them; the latter substance could, however, be arginine vasotocin. Data are presented suggesting that the association between the biosynthesis of neurophysin I and AVP on the one hand, and neurophysin II and OT on the other hand is maintained in patients with isolated AVP deficiency on the basis of a congenital defect.