Abstract: A method of determining the presence or onset of capillary leakage includes introducing into the blood stream of the subject a first low dosage of a low molecular weight macromolecular material and determining the volume of distribution thereof (an apparent volume of distribution). The determined value of volume of distribution is influenced not only by extravasation through the capillary wall but also by binding of smaller molecules to pores or receptor binding sites in the wall which occurs much faster than extravasation and is an important indicator of the onset of capillary leakage. The process is repeated with a high dose of high molecular weight macromolecular material to determine a further volume of distribution (the true circulating plasma volume). The two values are compared to determine the presence or onset of capillary leakage.