Interstitial fluid hydrostatic pressure (Pif) was measured with micropipettes during the acute edema generation that followed thermal skin injury in rats. Intradermal Pif was reduced from normal level of -1 mmHg to very negative values after thermal injury. The strongly negative Pif reflects a tissue imbibition pressure created by the thermal injury. The magnitude and duration of this pressure was dependent on the extent of the injury and the availability of fluid. After in vivo injury to 10 and 40% of the total body surface area (TBSA), mean intradermal Pif was temporarily reduced to -20 and -31 mmHg, respectively. Intravenous fluid infusion resulted in a rapid return of Pif to slightly positive values. Fluid available for transfer from the circulation was reduced by inducing the injury after killing the animal (postmortem injury) and even more by the subcutaneous insertion of a plastic barrier: this led to more pronounced reductions in Pif to average minimum values of -95 and -135 mmHg, respectively. Our data show that increased tissue imbibition pressure and increased net filtration pressure (tissue mechanisms) are responsible for a major part of the acute fluid shifts into thermally injured skin. Vascular mechanisms (permeability changes and intravascular pressure) are involved in the postburn edema development but are clearly less important than hitherto believed.