A major factor that affects solute and water transport through tissue is the state of tissue hydration. The amount of interstitial water directly affects the transport coefficients for both diffusion and convection. To investigate the effect of simultaneous exposure of tissue to hydrostatic and osmotic pressures on the state of tissue hydration and the pattern of distribution of tissue water, we dialyzed rats with isotonic (290 mosmol/kg) or hypertonic (510 mosmol/kg) solution at intraperitoneal pressures (P(ip)) between 0 and 6 mmHg, and we infused isotopic markers intravenously and determined their equilibrium distribution volumes (V(D)) in the anterior abdominal muscle (AAM) by quantitative autoradiography. Total tissue water volume (theta(TW)) was determined from dry-to-wet weight ratios. theta(urea), the V(D) of [(14)C]urea, equals the sum of the extracellular water volume (theta(EC), V(D) of [(14)C]mannitol) and intracellular water volume (theta(IC) = theta(urea) - theta(EC)). If theta(if) = interstitial water volume and theta(IV) = vascular water volume (V(D) of (131)I-labeled IgG), then theta(EC) = theta(if) + theta(IV). AAM hydrostatic pressure profiles were measured by a micropipette/servo-null system and demonstrated that elevation of P(ip) above 3 mmHg significantly (P < 0.05) increases mean tissue pressure (P(T)) to the same level regardless of intraperitoneal osmolality. The increase in P(T) resulted in a nonlinear tissue expansion primarily in the interstitium regardless of osmolality. From 0 to 6 mmHg, theta(if) (in ml/g dry tissue) increased from 0.59 +/- 0.02 to 1.7 +/- 0.05 and to 1.5 +/- 0.05 after isotonic and hypertonic dialysis, respectively, whereas theta(IC) increased from 2.8 +/- 0.08 to 3.0 +/- 0.1 after isotonic dialysis and decreased to 2.6 +/- 0.1 after hypertonic dialysis. After dialysis at 6 mmHg with isotonic or hypertonic solutions, theta(IV) increased from 0.034 +/- 0.001 to 0. 049 +/- 0.001 and 0.042 +/- 0.002, respectively. theta(urea) during hypertonic dialysis at P(ip) between 0 and 6 mmHg increased in a nonlinear fashion (F = 26.3, P < 0.001), whereas theta(IC) invariably decreased (F = 11.1, P < 0.001) and theta(if) doubled from its control value at low P(ip). In conclusion, elevation of intraperitoneal hydrostatic pressure causes tissue expansion, primarily in interstitium, irrespective of osmolality of the bathing solution. Tissue hydrostatic pressure is therefore the primary determinant of tissue properties with respect to hydration, which in turn affects diffusive and convective transport.