The aim of this study was to define the post-traumatic changes in body fluid compartments and to evaluate the effect of plasma colloid osmotic pressure (COP) on the partitioning of body fluid between these compartments. Forty-two measurements of plasma volume (green dye), extracellular volume (bromine), and total body water (deuterium) were done in ten traumatized patients (mean Injury Severity Score, ISS, = 34) and 23 similar control studies were done in eight healthy volunteers who were in stable fluid balance. Interstitial volume, intracellular volume, and blood volume were calculated from measured fluid spaces and hematocrit; COP was directly measured. Studies in volunteers on consecutive days indicated good reproducibility, with coefficients of variation equal to 3.5% for COP, 6.3% for plasma volume, 4.5% for extracellular volume, and 4.9% for total body water. COP values extended over the entire range seen clinically, from 10 to 30 mmHg. Interstitial volume was increased by 55% in patients, but intracellular volume was decreased by 10%. We conclude (1) that posttraumatic peripheral edema resulting from hemodilution is located in the interstitial compartment, with no intracellular space expansion; and (2) that interstitial volume, but not intracellular volume, is closely related to plasma COP.