Human hypoxanthine-guanine phosphoribosyltransferase manifests distinct kinetic, physical, and immunologic properties. A comparison of the normal and spontaneously occurring mutant forms of the enzyme indicates that its deficiency results from a large number of different mutations on a structural gene which is located within the X chromosome. This striking genetic heterogeneity is associated with the development of two distinctive clinical syndromes, the Lesch-Nyhan syndrome and a specific sub-type of gout.