Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) has been purified 23,000-fold from normal human erythrocytes. The purification includes affinity chromatography on a GMP column. The subunit molecular weight of the enzyme obtained from this purification is 24,000. The finding of four protein species after cross-linkage of the highly purified enzyme with dimethylsuberimidate, dimethyladipimidate, and glutaraldehyde suggests that the enzyme may exist in the native state as a tetramer.