BACKGROUND The role of the intestitium (the extracellular and extravascular tissue) with regard to transcapillary fluid balance and control of interstitial fluid volume has normally been considered to be a "passive controller". MATERIAL AND METHODS This review is based upon literature collected through the authors' own studies and through Medline searches. RESULTS Recent studies, however, indicate that the connective tissue cells can actively modulate physical properties of the interstitial matrix, so that it becomes an "active" participant in transcapillary fluid exchange and thereby interstitial fluid homeostasis. The beta 1-integrin system seems to provide a common pathway by which the cells can raise and lower interstitial fluid pressure and thereby regulate the tissue fluid volume. INTERPRETATION Experiments in which a new anti-inflammatory agent (alpha-trinositol), platelet-derived growth factor (PDGF), and a prostagladin F2 alpha-analog (latanoprost) modulate interstitial fluid pressure and oedema generation in acute inflammation, suggest that the extracellular matrix can be a target for pharmacological intervention during inflammatory processes.