We studied the effect of sleeping in the head-up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150-200 mmol Na+ d-1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P less than 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from -64/-42/-25 +/- 29/21/17 mmHg to -53/-37/-23 +/- 31/24/20 mmHg (P less than 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from -63/-40/-24 +/- 20/12/11 mmHg to -21/-19/-8 +/- 12/10/5 mmHg (P less than 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 +/- 9/8/7 mmHg initially to 95/69/57 +/- 27/22/20 mmHg during combined treatment (P less than 0.05 for systolic and mean BP), and remained unchanged during the 14-month (range 8-70 month) follow-up period. Nocturnal sodium excretion decreased from 8.0 +/- 2.3 mmol h-1 to 5.9 +/- 1.9 mmol h-1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5-2.4 kg) (P less than 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo-adrenergic orthostatic hypotension.