The effect of fluid volume loading on lung tissue fluid compartments and pulmonary lymph flow was studied in 7 dogs. A bolus of 125I-labeled albumin was administered 1 h after a 10--15% body weight Tyrode infusion. Then concentrations of labeled and endogenous albumin in pulmonary lymph and plasma were monitored for 4--6 h. The time course of plasma and lymph [125I]albumin specific activities was analyzed using kinetic and both the linear and nonlinear solute flux equations. Plasma specific activity exhibited a two-component decay with mean rate constants of 2.65 and 0.071 h-1. Albumin equilibrated between plasma and lymph at a rate of 0.327 h-1, or with a half time of 2.12 h. For albumin, the mean permeability-surface area product was 0.043 ml/min, and total distribution volume was 22.6 ml. This indicated that the cannulated lymphatics drained 25% of total lung weight, and that lung lymph flow was 0.063 ml . min-1 . 100 g-1 in normally hydrated lungs, and 0.225 ml . min-1 . 100 g-1 in edematous lungs. During edema the extravascular 99mTc-DTPA (diethylenetriamine pentaacetic acid) space increased by 79% and the total extravascular lung water by 40%. The extravascular albumin space was only one-third that predicted for the extent of edema. This indicates a significant volume of edema fluid sequestered in tissue compartments, such as perivascular cuffs and alveolar spaces, which did not equilibrate rapidly with capillary filtrate draining into the pulmonary lymphatics.