Recent permeability studies comparing endothelial cell phenotypes derived from alveolar and extra-alveolar vessels have significant implications for interpreting the mechanisms of fluid homeostasis in the intact lung. These studies indicate that confluent monolayers of rat pulmonary microvascular endothelial cells (RPMVEC) had a hydraulic conductance (Lp) that was only 5%, and a 72 kD dextran transendothelial flux rate only 9 % of the values determined for rat pulmonary artery endothelial cell (RPAEC) monolayers. Based on previous studies partitioning the filtration coefficients between alveolar and extra alveolar vascular segments in rat lungs, and previous studies of lymph albumin fluxes and permeability, the contribution of the alveolar capillary segment to total albumin flux in lymph was estimated to be less than 10%. In addition, the Starling safety factors against the edema calculated for alveolar capillaries would be quite different from those estimated for whole lung. Based on the Lp for RPMVEC, the edema safety factor due to the pressure drop required for increased filtration would be quantitatively the greatest safety factor across the alveolar capillaries, but a minor safety factor for extra-alveolar vessels. Also, a markedly higher effective protein osmotic absorptive pressure for plasma proteins must occur in the capillaries relative to extra-alveolar vessels. The lower Lp for alveolar capillaries also has implications for the sequence of hydrostatic edema formation and it also may have a role in preventing exercise induced alveolar flooding.