An experimental study was made on the distribution of solutes between articular cartilage and external solution, and on their diffusivity in cartilage. The solutes were classed as small ions, small uncharged molecules, and uncharged molecules of increasing size ranging from glucose to hemoglobin. The distribution of sodium and chloride ions obeys the Donnan equilibrium when cartilage is equilibrated in physiological saline solution. However, in cartilage immersed in dilute solution the concentration of chloride ions is higher than predicted. This is probably due to the presence in cartilage of some microscopic regions depleted of mucopolysaccharide in which the Donnan exclusion does not operate. The molal distribution coefficients of small uncharged molecules like urea are close to unity, which indicates that all water in cartilage seems to behave as solvent water. For larger molecules the distribution as well as the diffusion coefficients decrease with increase in molecular weight and are very sensitive to variations in fixed charge density. The results have been interpreted on the basis of the “steric exclusion” principle. The largest molecules which can penetrate into cartilage are of the size of the hemoglobin molecule.