Five families with the Lesch-Nyhan syndrome (LNS) and two families with the Kelley-Seegmiller syndrome (KSS) were studied. Seven different mutations were identified. Two transitions, C526?T (Pro176Ser) and G481?A (Ala161Thr), in patients with a milder form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency were detected. In patients with the Lesch-Nyhan syndrome two transitions, G569?A (Gly190Glu) and C508?T (Arg170Ter), two transversions, C222?A (Phe74Leu) and C482?A (Ala161Glu), and a deletion of seven nucleotides (from A394 to G400) were observed. All except two of the identified mutations are novel. The C222?A substitution in exon III is located within one of the clusters of hot spots of the HPRT gene and has been previously described in four unrelated patients. The other recurrent mutation C508?T in exon VII has been reported in eight families.