Symptomatic hypotension during hemodialysis is a disabling complication in end-stage renal disease (ESRD) patients, especially in certain groups of patients who are at higher risk for this problem. Autonomic dysfunction is thought to play a significant role. We evaluated the efficacy of midodrine, an oral agent with selective alpha-adrenergic agonist activity used in the treatment of neurogenic orthostatic hypotension, on 10 hemodialysis patients with persistent intradialytic hypotension. The patients were given a dose of midodrine (mean dose, 5.5 mg; range, 5 to 10 mg) 30 minutes before each hemodialysis session. We compared blood pressure, pulse, body weight, and laboratory values for 10 consecutive dialysis sessions off and on midodrine therapy. There was a statistically significant improvement in lowest intradialytic systolic blood pressure (from 96.6 to 114.7 mm Hg; P < 0.001), lowest intradialytic diastolic blood pressure (from 53.2 to 59.0 mm Hg; P = 0.002), lowest intradialytic mean arterial pressure (from 67.7 to 77.6 mm Hg; P < 0.001), posthemodialysis systolic blood pressure (from 116.5 to 127.1 mm Hg; P < 0.001), posthemodialysis diastolic blood pressure (from 66.6 to 69.7 mm Hg; P = 0.040), and posthemodialysis mean arterial pressure (from 83.2 to 88.8 mm Hg; P = 0.001) after patients were placed on midodrine. There also was a small but statistically significant decrease in intradialytic pulse rate (from 86.3 to 81 beats/min; P = 0.021) and posthemodialysis pulse rate (from 87.4 to 81.7 beats/min; P = 0.024) after initiation of midodrine therapy. There was no significant difference in any of the prehemodialysis blood pressure measurements or pulse rate off or on midodrine therapy. The improvements in intradialytic and posthemodialysis blood pressure were associated with a uniform subjective improvement in symptoms associated with dialysis hypotension, such as cramps, fatigue, dizziness, and weakness. Other than scalp paresthesia in one patient, no adverse effects were noted. Our results suggest that the administration of a single dose of midodrine before hemodialysis is an effective therapy for intradialytic hypotension. A prospective trial with adequate patient numbers and long-term follow-up would be useful to evaluate this drug's efficacy and safety profile in patients with ESRD.