Abstract.Freezing and thawing of dilute normal human fibroblast suspensions causes partial inactivation of hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) and adenine phosphoribosyltransferase (APRT). Phosphoribosyl‐pyrophosphate (PRPP) stabilizes both phosphoribosyltrans‐ferases against this inactivation. Mutant HGPRT enzymes from a patient with the Lesch‐Nyhan syndrome and from a gouty patient with partial HGPRT deficiency were similarly inactivated by freezing and thawing, but only the former mutant enzyme could be stabilized by PRPP. The insensitivity of the mutant HGPRT from the patient with partial enzyme deficiency to PRPP stabilization indicates a structural enzyme alteration. The different sensitivity of the two HGPRT mutants to PRPP stabilization reflects the heterogeneity of HGPRT mutations