OBJECTIVE: To determine the involvement of nitric oxide production in hemodialysis-induced hypotension. DESIGN: Examination of nitric oxide synthesis, cyclic guanosine 3'5'-monophosphate (cGMP) levels, and endothelin-1 levels in plasma before and after hemodialysis. SETTING: Veterans Affairs medical center. PATIENTS: 13 patients with end-stage renal failure who were receiving hemodialysis: Six patients had hypotensive episodes during dialysis and 7 did not. INTERVENTION: Patients received heparin at a bolus dose of 2000 U at the initiation of dialysis followed by 1000 U/h during 4-hour hemodialysis sessions. RESULTS: Nitric oxide production markedly increased during hemodialysis-induced hypotensive episodes; this increase was not seen in patients who did not have a hypotensive episode. In both groups, the plasma cGMP and endothelin-1 levels decreased after hemodialysis. According to multiple regression analysis, standard coefficients of nitric oxide production, plasma cGMP levels, and endothelin-1 levels with mean blood pressure after hemodialysis were -0.743, -0.07, and 0.31, respectively. CONCLUSION: Nitric oxide production increased in patients who had a hypotensive episode during hemodialysis but did not increase in those who did not have a hypotensive episode.