The etiologic role of renin-angiotensin system and sodium-volume status in the pathophysiology of various forms of hypertension was investigated. Plasma renin activity (PRA) was measured by radioimmunoassay, while sodium-volume status was evaluated by the determination of total exchangeable sodium(NaE) using isotope dilution method. The subjects consisted of 25 controls, 24 patients with essential hypertension, 22 patients with chronic renal failure (13 with hypertension, 9 without hypertension) and 14 patients with malignant hypertension. The results were as follows: 1) An inverse correlation between NaE and PRA was noted in control subjects (r=-0.598, p<0.001) and normal renin essential hypertension(r=-0.551, p<0.05) and the chronic renal failure with hypertension. (r=-0.790, P<0.001) 2) NaE increased markedly the in chronic renal failure with hypertension (66.9¡¾8.69mEq/kg of LBM, p<0.001) and the chronic renal failure without hypertension (54.9¡¾9.28 mEq/kg of LBM, p<0.05), while mild increase was noted in malignant hypertension (51.7¡¾6.24mEq/kg of LBM, 0.050.1) 3) Absolute value of PRA was not deviated significantly from control group (2.53¡¾1.416 ng/ml/hr) except in malignant hypertension (6.09¡¾2.042, p<0.001). But PRA was inappropriately high in relation to prevailing NaE in the chronic renal failure with hypertension (eleven of thirteen patients) and malignant hypertension (ten of fourteen patients), while PRA variatiation was within physiologic range in the chronic renal failure without hypertension. 4) The NaE-PRA product was markedly increased in the chronic renal failure with hypertension (514.4¡¾42.10, p<0.001) and in malignant hypertension (442.7¡¾55.03, p<0.001), while moderately increased NaE-PRA product was noted in the chronic renal failure without hypertension (402.6¡¾59.67, p<0.001). No significant difference in NaE-PRA product was noted in essential hypertension (354.4¡¾62.38, p>0.1). It is suggested that renin-angiotensin system plays a predominant role in the pathogenesis of malignant hypertension and in hypertension of chronic renal failure, though sodium retention is also contributing factor. PRA variation in essential hypertension does not appear to be associated with any consistent change in Na-volume status, suggesting the existence of another mechanism in the genesis of hypertension and PRA variation.