The rational choice of a plasma substitute for states of hypovolaemia depends partly on its colloid osmotic pressure (COP). We have measured the COP of 108 samples of plasma substitute across selectively permeable membranes which retain molecules greater than 10,000 dalton (COP10) and 50,000 dalton (COP50) the ratio COP50/COP10 providing a potential index of diffusibility of the smaller molecules across capillary membranes. 6% Hespan solution showed a particularly favourable COP50/COP10 ratio at 0.58 indicating a potential for good retention in the circulation whilst 3.5% Haemaccel showed a COP50/COP10 ratio of 0.18 indicating a potential for marked transcapillary diffusion, especially in states of capillary leak. In patients with normal capillary permeability both Gelofusine and Dextran 110 are likely to show adequate retention in the circulation with a COP50/COP10 ratio of 0.37 and 0.39 respectively. These are comparable to the retention of 4.5% human albumin (0.36) but all of the plasma substitutes tested, with the exception of Haemaccel, provided a higher COP across both membranes than 4.5% human albumin solution. An in vivo comparison of these plasma substitutes is required to confirm the advantages of macromolecular colloids in states of capillary leak.