The modifications of the macromolecular sieving properties of the pulmonary extracellular tissue matrix were studied in adult anaesthetized rabbits (n = 10) exposed to increased tissue hydration. Exclusion of albumin from the perivascular pulmonary interstitial space was determined by using the continuous infusion method coupled with direct sampling of interstitial fluid performed through the wick technique. The rabbits underwent an intravenous infusion of saline amounting to 10 (n = 5) or 20 % (n = 5) body weight. Extracellular albumin distribution volume was derived from the steady state tissue concentration of radioactive rabbit serum albumin (125I-RSA). Pulmonary extracellular and intravascular fluid volumes (Vx and Vv, respectively) were measured as distribution volumes of 51Cr-EDTA and 131I-RSA, respectively, and interstitial fluid tracer concentrations were determined in interstitial fluid collected through implanted wicks. At the highest degree of hydration, interstitial fluid volume (Vi = Vx - Vv) and extravascular albumin distribution volume (Va,w) significantly increased by 38.5 and 240.2 %, respectively, compared to control. Albumin-excluded volume (Ve,a = Vi - Va,w) was 398.9 +/- 17 microl (g dry tissue weight)-1; the albumin-excluded volume fraction (Fe,a = Ve,a/Vi) was 0.23 +/- 0.01, 33.2 % of the control value. Data indicate that, at variance with what is observed in tissues like skin and muscle, pulmonary Fe,a is highly sensitive to tissue fluid content.