The role of arginine vasopressin (AVP) in malignant renal hypertension was investigated using the homozygous Brattleboro (vasopressin-deficient) rat. Brattleboro rats with complete aortic-ligature between the renal arteries developed malignant hypertension with the same frequency and severity as normal Long-Evans rats subjected to the same procedure. The Long-Evan's hypertensive rats had significantly elevated plasma AVP levels. Plasma renin activity and plasma angiotensin II levels were significantly elevated in both Brattleboro and Long-Evans rats with malignant hypertension and the levels reached were equivalent in both groups. Thus, the renin-angiotensin system did not compensate for the lack of AVP in malignant hypertensive Brattleboro rats. Specific vascular lesions of fibrinoid necrosis were observed in a high percentage of rats with malignant hypertension, in both the Brattleboro and Long-Evans strains. We conclude that AVP does not play a primary role in the pathogenesis of malignant renal hypertension and, in particular, in the development of the vascular lesions of fibrinoid necrosis.