The individual processes involved in interstitial fluid volume and protein regulation-microvascular filtration, lymphatic return, and interstitial storage-are relatively simple, yet their interaction is exceedingly complex. There is a notable lack of a first-order, algebraic formula that relates interstitial fluid pressure and protein to critical parameters commonly used to characterize the movement of interstitial fluid and protein. Therefore, the purpose of the present study is to develop a simple, transparent, and general algebraic approach that predicts interstitial fluid pressure (P_i) and protein concentrations (C_i) that takes into consideration all three processes. Eight standard equations characterizing fluid and protein flux were solved simultaneously to yield algebraic equations for P_i and C_i as functions of parameters characterizing microvascular, interstitial and lymphatic function. Equilibrium values of P_i and C_i arise as balance points from the graphical intersection of transmicrovascular and lymph flows (analogous to Guyton's classical cardiac output-venous return curves). This approach goes beyond describing interstitial fluid balance in terms of conservation of mass by introducing the concept of inflow and outflow resistances. Algebraic solutions demonstrate that P_i and C_i result from a ratio of the microvascular filtration coefficient (=1/inflow resistance) and effective lymphatic resistance (=outflow resistance) and P_i is unaffected by interstitial compliance. These simple algebraic solutions predict P_i and C_i that are consistent with reported measurements. The present work therefore presents a simple, transparent, and general balance point characterization of interstitial fluid balance resulting from the interaction of microvascular, interstitial and lymphatic function.