Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, the fluid balance equations must be solved numerically, limiting the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, our solution is formulated as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "Edemagenic Gain" is a function of microvascular fluid permeability (K_f), effective lymphatic resistance (R_L) and interstitial compliance (C). This formulation suggests two types of gain: "Multivariate" dependent on C, R_L, and K_f, and "Compliance-Dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how Edemagenic Gain is altered with pulmonary edema induced by venous hypertension, histamine and endotoxin. Reformulation of the classical equations governing fluid balance in terms of Edemagenic Gain thus yields new insight into the factors affecting an organ's susceptibility to edema.