Fluid loss from the peritoneal cavity to surrounding tissue varies directly with intraperitoneal hydrostatic pressure (Pip). According to Darcy's law [Q = -KA(dPif/dx)], fluid flux (Q) across a cross-sectional area (A) of tissue will increase with an increase in either hydraulic conductivity (K) or the interstitial fluid hydrostatic pressure gradient (dPif/dx, where x is distance). Previously, we demonstrated that in the anterior abdominal muscle (AAM) of rats, dPif/dx increases by only 40%, whereas K rises fivefold between Pip of 1.5 and 8 mmHg. Because K is a function of interstitial volume (thetaif), we hypothesized that perturbations of Pip would change Pif and expand the interstitium, increasing thetaif. To test this hypothesis, we used dual-label quantitative autoradiography (QAR) to measure extracellular fluid volume (thetaec) and intravascular volume (thetaiv) in the AAM of rats within the Pip range from -2.8 to +8 mmHg. thetaif was obtained by subtraction (thetaec - thetaiv). dPif/dx was measured with a micropipette and a servo-null system. Local thetaiv did not vary with Pip and averaged 0.010 +/- 0.002 ml/g, and thetaif averaged 0. 19 +/- 0.01 ml/g at Pif 0.001) in the SC. We conclude that the mechanisms responsible for the increase in K with Pip include expansion of the interstitium, dilution of interstitial macromolecules, and washout from the AAM to SC of interstitial macromolecules responsible for resistance to fluid flow.