High-frequency single nucleotide polymorphism (SNP) alleles are useful in mapping genes responsible for disease susceptibility. Functionally, Fcgamma receptors (FcgammaR) have been implicated in autoimmune disease, and the gene encoding the signaling element for several FcgammaR, Fc-epsilon-receptor gamma-chain (FcepsilonRIgamma), has several SNPs in the immunoreceptor tyrosine activation motif (ITAM) recorded in GenBank. Direct sequencing of the FcepsilonRIgamma coding region found potentially polymorphic sites in the 5'-->3' direction in control donors, which were not confirmed in the reverse direction (n = 66), and further exploration of 80 SLE patients revealed no non-synonymous SNPs. One normal donor was heterozygous for a non-synonymous SNP at nt 38 which changed the fifth codon from valine (GTG) to methionine (ATG). Although the EST databases suggest candidate SNPs, insertions and deletions, these appear to be artifacts, most probably due to secondary structure. The coding region of FcepsilonRIgamma shows a remarkable absence of nucleotide diversity. Either as yet unidentified regulatory elements of FcepsilonRIgamma or other genes in the region of human chromosome 1q23 are likely to be systemic lupus erythematosus disease susceptibility and severity genes.