Fluid balance at the capillary level has been simulated with an analogue computer program, based on experimental data on regional differences in capillary permeability, surface areas, and hydrostatic pressures. The program takes into account fluid and protein fluxes into and out of the interstitial space. Solutions are obtained for tissue hydrostatic pressure, tissue fluid osmotic pressure, interstitial space volume, and lymph flow. Simulation of a variety of physiological experiments and clinical disease states has yielded reasonable agreement between experimental data and data obtained by computer analysis. Dilution of the interstitial plasma protein pool with a consequent reduc6tion of its oncotic pressure appears to be a major factor, which prevents edema unless plasma oncotic pressures are reduced by 10-15 mm Hg or, alternatively, venous pressures are elevated by a similar amount. The computer analysis in all instances yields positive values for tissue pressure, in agreement with experimental data obtained by needle puncture. The negative tissue pressures observed in subcutaneous capsules can be reproduced in the computer program, if the interface between the capsule and the surrounding interstitial space is assumed to have the properties of a semipermeable membrane.