1. Overnight recumbent and upright plasma atrial natriuretic peptide (ANP) levels were markedly elevated (P less than 0.001) in patients with orthostatic hypotension (OH). 2. Overnight urinary clearance of ANP was significantly lower (P less than 0.01) in patients with OH, and was inversely correlated with plasma ANP levels (r = -0.94, P less than 0.01). The same negative correlation (r = -0.87, P less than 0.01) was seen in normal subjects. 3. Reduced urinary clearance of ANP may be associated with reduced filtered load and increased binding of ANP to the neutral endopeptidase 24.11 receptor binding sites in the proximal renal tubule. 4. ANP may be involved in the pathophysiology of orthostatic hypotension.