Protein tyrosine phosphatase non-receptor 22 (PTPN22) is involved in the negative regulation of T-cell responsiveness. Recently, it has been reported that a single nucleotide polymorphism (SNP), C1858T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), is associated with an increased risk of a number of autoimmune diseases. To study the mutant frequency and polymorphism of PTPN22 in Chinese populations, 1085 individuals from 15 Chinese populations distributing widely from north to south were collected. The genotypes of PTPN22-C1858T were determined by polymerase chain reaction-restriction fragment length polymorphism with the digestion of restriction endonuclease RsaI. Of the 1085 individuals, 31 of whom were heterozygote (PTPN22-1858C/T), the frequency of PTPN22-1858T allele in those tested individuals was 1.43%. Moreover, the frequencies of PTPN22-1858T had significant variance in 15 populations of China (chi(2) = 74.1650, P < 0.01).