The relationship between tissue hydrostatic pressure and fluid content is an important determinant of the response of the microvascular exchange system to perturbations. However, only a limited number of studies relating these parameters have been reported. To add to this body of information, fully swollen rat dermis in vitro was subjected to successive compressive loads in an apparatus in which tissue thickness changes were monitored. At steady-state the mechanical load on the tissue was balanced by the interstitial fluid pressure within the tissue while the fluid content of the tissue was determined from the unstressed tissue fluid content and changes in tissue thickness. The range of conditions investigated was from moderate overhydration through normal tissue fluid content to significant dehydration. From the relationship between interstitial fluid pressure and tissue fluid content (expressed as mass of fluid per mass of fat-free dry tissue) the tissue compliance was determined. Compliance, defined as the rate of change of the tissue fluid content with changes in interstitial pressure, increased with tissue hydration. The compliance determined using compressive loads and steady-state response of tissue thickness compares favourably with the limited amount of information available about this tissue property which is critical in the determination of tissue fluid balance. Compliance ranged over one order of magnitude for the conditions studied and at normal hydration, tissue fluid volume changed by about 6.6% per mmHg in tissue hydrostatic pressure.