A theoretical description of the mechanics of the interstitium is used to derive a relation for interstitial fluid pressure. The nature of this relation is examined and the dependence of fluid pressure on imbibed fluid, free fluid, and osmotic balances is defined. When the theory is applied to an idealized osmometer configuration, the predicted pressure-volume curve is analogous to the experimental observations of A. C. Guyton (1965, Circ. Res., 16, 452-460). Further, it is suggested that the similarity between the present theory and the experimental data of Guyton supports the hypothesis that a negative interstitial pressure and a dearth of free fluid is an expected and perhaps dominant state of normal tissue.