Docetaxel and prostaglandin E1 (PGE₁) increase transcapillary protein extravasation and reduce interstitial fluid pressure in skin. In this study the microdialysate concentration (C_m) of ¹²⁵I-Human serum albumin (¹²⁵I-HSA) and different sized endogenous plasma proteins (EPP) was compared to evaluate changes in transcapillary extravasation of plasma proteins. ¹²⁵I-HSA was also used to estimate changes in specific activity of albumin. Extravasation of ¹²⁵I-HSA and EPP from plasma to interstitium in rat skin was compared during continuous administration of docetaxel and PGE₁ by using microdialysis in anesthetized rats. Also, 20 ml of Ringer's solution (RS) was injected intravenously over 10 min in a separate group. Two hollow plasmapheresis fibers (3 cm, cut off 3000 kDa), one acting as control, were placed subcutaneously on back skin and perfused with RS (5 µl/min, 140 min, collected every 10 min). The size of the different EPP were estimated to be 73, 65, 56, 47 and 39 A, separated by a size-exclusion HPLC column and quantified by UV detection (280 nm). Docetaxel (0.5 mg/ml, n=5) increased C_m of ¹²⁵I-HSA and EPP of size 73, 65, 56 and 39 A significantly (p<0.05) compared to control. PGE₁ (20 µg/ml, n=6) increased C_m of ¹²⁵I-HSA significantly (p<0.05), but none of the different sized EPP compared to control. Intravenous RS (20 ml, n=6) increased C_m of ¹²⁵I-HSA and all the different sized EPP significantly (p<0.05) compared to control. Although the microdialysis method is able to monitor qualitative changes in capillary permeability, a quantitative determination of the capillary reflection coefficient or PS product was not possible, since steady-state between plasma and dialysate was not achieved during the measurement period. The different pattern of extravasation of EPP and ¹²⁵I-HSA after docetaxel, PGE₁, and RS indicates increased interstitial transport rate and/or increased capillary permeability after docetaxel and RS, while PGE₁ increased transcapillary fluid flux without altering the permeability.