Intradialysis hypertension is a frustrating complication among hemodialysis (HD) patients. This study was conducted to investigate the physiological changes during intradialytic hypertension. The beat-to-beat continuous heart rate, hematocrit (Hct) changes during HD, serum levels of nitric oxide, plasma levels of catecholamine, renin, endothelin (ET-1), cardiac output (CO), and peripheral vascular resistance (PVR) were measured before and after HD in patients prone to develop intradialysis hypertension (n = 30) and from age, sex-matched control HD subjects (n = 30). It was found that the baseline values of Hct, serum levels of nitric oxide, plasma levels of catecholamine, renin, and ET-1, CO, PVR, and power index (low frequency/high frequency ratios) of heart rate variability were not significantly different between the patients and control subjects. In the hypertension-prone group, the plasma levels of catecholamine, renin, and the serial measurements of power index, did not show significant changes. However, the patients showed a significant elevation of systemic vascular resistance (56.8 +/- 9.2% vs 17.7 +/- 9.5; P < 0.05), ET-1 (510.9 +/- 43.3 vs 276.7 +/- 30.1 pg/ml; P < 0.05) and a significant decrease of nitric oxide (NO)/ET-1 balance (0.018 +/- 0.003 vs 0.034 +/- 0.005; P < 0.05) at the end of HD compared with the control patients. It was found that the physiological changes in intradialysis hypertension patients were characterized by inappropriately increased PVR through mechanisms that did not involve sympathetic stimulation or renin activation but might be related with altered NO/ET-1 balance.