OBJECTIVE Hyperkalemic responses to both physical exercise and alpha-adrenergic stimulation are enhanced in patients with terminal renal failure. Alpha-adrenergic blockade was found to protect against hyperkalemia during vigorous exercise in healthy men. The aim of the study was to examine the effects of the alpha-adrenergic blocker doxazosin on exercise-induced hyperkalemia in hemodialysis patients. METHODS In a randomized, placebo-controlled, crossover design study, 15 anuric, chronic hemodialysis patients were included. Doxazosin or placebo was given in a random order for 4 days before exercise. At the end of each phase of the study, a 30-min treadmill exercise test with a constant workload of 2 metabolic equivalents was performed followed by a 30-min recovery period. RESULTS The patients achieved 64 +/- 3 and 62 +/- 3% of maximal heart rate during the exercise test on doxazosin and placebo, respectively. The baseline plasma concentration of potassium was similar both on active treatment and on placebo (5.1 +/- 0.2 mmol/l on doxazosin and 4.9 +/- 0.1 mmol/l on placebo). The serum potassium concentration increased significantly and to a similar extent during the tests. The mean rates of potassium increment during exercise were 8.4 +/- 1.5 micromol/l/min on doxazosin and 6.9 +/- 1.3 micromol/l/min on placebo. During the recovery period, the serum potassium concentration significantly decreased in both arms of the study. There were no significant changes in plasma sodium, calcium, and phosphate levels during the tests. Hydrogen ion concentration in blood, serum insulin and glucose, and plasma aldosterone and renin activity were similar before the exercise tests. CONCLUSIONS Alpha-adrenergic blockade does not modulate the hyperkalemic response to moderate physical exercise in patients with terminal renal failure.