Altering the balance between pro- and anti-inflammatory responses can influence an animal's susceptibility to acute or chronic inflammatory disease; bovine mastitis is no exception. Genetic variation in the form of single nucleotide polymorphisms (SNPs) may alter the function and expression of genes that regulate inflammation, making them important candidates for defining an animal's risk of developing acute or chronic mastitis. The objective of the present study was to identify SNPs in genes that regulate anti-inflammatory responses and test their association with estimated breeding values (EBVs) for somatic cell score (SCS), a trait highly correlated with the incidence of mastitis. These genes included bovine interleukin-10 (IL-10) and its receptor (IL-10R), and transforming growth factor beta1 (TGF-beta1) and its receptor (TGF-betaR). Sequencing-pooled DNA allowed for the identification of SNPs in IL-10 (n = 2), IL-10Ralpha (n = 6) and beta (n = 2), and TGF-beta1 (n = 1). These SNPs were subsequently genotyped in a cohort of Holstein (n = 500), Jersey (n = 83), and Guernsey (n = 50) bulls. Linear regression analysis identified significant SNP effects for IL-10Ralpha 1185C>T with SCS. Haplotype IL-10Ralpha AAT showed a significant effect on increasing SCS compared to the most common haplotype. The results presented here indicate that SNPs in IL-10Ralpha may contribute to variation in the SCS of dairy cattle. Although functional studies are necessary to ascertain whether these SNPs are causal polymorphisms or merely in linkage with the true causal SNP(s), a selection program incorporating these markers could have a beneficial influence on the average SCS and productivity of a dairy herd.