Interstitium contains a matrix of fibrous molecules that creates considerable resistance to water and solutes in series with the microvessel wall. On the basis of our preliminary studies (Adamson, 1994, Microcirculation1(4), pp. 251–265; Fu, 1995Am. J. Physiol.269(38), pp. H2124–H2140), by using laser-scanning confocal microscopy and a theoretical model for interstitial transport, we determined both microvessel solute permeability and solute tissue diffusion coefficient of -lactalbumin (Stokes radius ) from the rate of tissue solute accumulation and the radial concentration gradient around individually perfused microvessel in frog mesentery. is . for -lactalbumin is . This value of is comparable to that for small solute sodium fluorescein (Stokes radius ), while is only 3.4% of . Our results suggest that frog mesenteric tissue is much less selective to solutes than the microvessel wall.