Cell membrane preparations from spleens of surviving patients were treated by a series of steps that would lead, if the starting material had been mouse tissue, to soluble and highly purified H-2 transplantation antigens. The purified fractions from human tissue proved to have the specificity of HL-A (Hu-1) leucocyte group antigens that are known to play a major role in tissue graft rejection. The steps through which the H-2 and HL-A antigens showed exactly the same behaviour were: extraction of membrane lipoprotein, solubilization procedures, gel filtration separations and ion-exchange chromatography. The results indicate that human HL-A and mouse H-2 antigens are molecules with closely similar over-all composition. Serological tests show that the isolated HL-A antigens carry the correct specificities reflecting the original donor typing and do not carry specificities the donor did not possess. The soluble HL-A antigens are stable for at least 2 years when kept freeze-dried at −20 C. It is concluded that human leucocyte group antigens of the HL-A system are likely to be genetic homologues of the mouse H-2 antigens and hence that the extensive data that has accumulated from studies of the mouse model system may be used to guide further studies in man.