Overall transvascular escape rate of albumin [TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to the extravascular space per unit time] was determined from the disappearance of i.v. injected radioiodinated serum albumin. Patients with tense ascites due to liver cirrhosis and pigs with posthepatic portal hypertension and intraperitoneally instilled fluid were studied before and after abdominal paracentesis in order to evaluate the effect of ascitic fluid hydrostatic pressure on the transvascular escape rate of albumin. TERalb of the ascitic patients (n = 6) were on average 7.8% IVMalb.h-1, which is somewhat higher but not significantly above normal (mean 5.6% IVMalb.h-1). After paracentesis and removal of the ascitic fluid, TERalb rose significantly to an average of 11.9% IVMalb.h-1 (P less than 0.05). The fraction of IVMalb passing into the peritoneal cavity was on average 0.21 and 0.38% IVMalb.h-1 before and after paracentesis, respectively (n = 4). In ascitic, posthepatic portal-hypertensive pigs (n = 6), TERalb averaged 15.1% IVMalb.h-1, a value not being significantly different from non-ascitic, normotensive controls (mean 16.1% IVMalb.h-1). After paracentesis, TERalb rose significantly to an average of 24.3% IVMalb.h-1. The increased albumin extravasation rate after removal of ascites is best explained by an increased sinusoidal-tissue pressure difference caused by a decreased hydrostatic fluid pressure in the liver interstitium (portal and subcapsular spaces) due to the hydrostatic effect of the removed ascitic fluid.