Interleukin-10 (IL-10) production is genetically determined and influenced by different polymorphisms in the promoter region of IL-10. These polymorphisms may contribute to the risk and clinical outcome of various infectious and immunological-related diseases. The Samis are the aboriginal inhabitants of Norway and Fennoscandinavia and are ethnically different from the Norwegians. Different distribution of various immune-related diseases among the Samis compared with Norwegians have been reported. This is the first study to evaluate the distribution of IL-10 polymorphisms in the Sami population. Two hundred healthy Samis were genotyped for polymorphisms in the promoter region of IL-10 at region -1082 (G/A), -819 (T/C) and -592 (A/C). The allele frequencies, genotypes and haplotypes were compared with 187 healthy Norwegians. A significantly higher number of the Samis than the Norwegians had the ATA/ATA genotype, whereas the Norwegians displayed a higher frequency of the GCC/GCC genotype (P=0.0057). There was a significant difference in haplotypes in the two populations with a P=0.0024. These findings may be important for the distribution and clinical outcome of various infectious and immune-related disorders in the two populations.