In this study, disturbance of immune response as a pathogenic mechanism for human volume hypertension was investigated and compared to nephritis in its correlation with the metals such as zinc, iron and aluminum as environmental factors. Urinary gamma-GTP excretions in patients with nephritis or hypertension were higher than in healthy people, whereas the plasma renin activity in these patients were lower on the average than in healthy individuals. Hypertensive patients participating in this study were diagnosed as the volume hypertension type from our clinical and other results. The serum IgM and IgA levels in renal patients showed a tendency to be lower than in the healthy people used as control. Urinary IgA excretion in hypertensive patients was increased in association with increasing excretions of aluminum and/or iron into urine. The values of regression coefficients in the urine samples for aluminum and iron vs. IgA, respectively, were very high at r = 0.900 (n = 9, p < 0.05) and 0.736 (n = 9, p < 0.05). These correlations were shown to be very useful indicators in diagnosing volume hypertension. Moreover, hypertensive patients in this study were demonstrated to have a high regression coefficient (r = -0.702, n = 7; p < 0.05) for calcium vs. renin in the serum. In the hypertension, augmentation of serum calcium significantly decreased plasma renin activity.