Low-dose infusions of atrial natriuretic peptide (ANP) into humans reduce cardiac filling pressures without enhancing renal excretion or producing vasodilation. The present human study was undertaken to seek an effect of ANP on capillary filtration in humans and to determine its relationship to reductions in cardiac filling pressures. Heart rate (electrocardiogram), blood pressure (cuff method), and renal excretion of salt and water were determined, and central venous pressure (jugular vein cannulation, strain-gauge transducer) and forearm venous compliance and capillary filtration coefficient (strain-gauge plethysmography) were derived by computer. Forearm girth and venous pressure (peripheral vein catheter) measurements were obtained while the arm was elevated above heart level, and an upper arm blood pressure cuff was intermittently inflated to venous occluding pressures of 20, 30, and 40 mmHg. Forearm measurements, hematocrit, plasma proteins, albumin and plasma levels of ANP were determined from euvolemic volunteers before and during 60 min intravenous infusions of ANP (5 ng.kg-1.min-1, n = 9) or placebo (isotonic saline, n = 7). ANP infusions produced physiological increases (4- to 5-fold) in plasma ANP (from a base line 35 +/- 6 pg/ml) (P less than 0.05). Hemodynamic responses to ANP consisted of a reduction in central venous pressure (P less than 0.05) and no change in heart rate, mean arterial pressure, or renal excretory parameters. ANP increased forearm capillary filtration between 37 and 63% (P less than 0.05) from base line but did not significantly alter forearm compliance measurements.(ABSTRACT TRUNCATED AT 250 WORDS)