Genetic variants in a number of immunoregulatory genes have been previously associated with health and production traits in dairy cattle. Therefore, in the following study, the genes coding interferon gamma (IFNG), IFNG receptor 1 and 2 domains, interleukin-22 (IL22), and IL22 receptor alpha 1, were investigated for single nucleotide polymorphisms (SNPs) in Holstein bulls. These SNPs, along with SNPs previously identified in IL10, IL10 receptor, and transforming growth factor beta 1 (TGFB1) genes, were evaluated for statistical associations to estimated breeding values for milk somatic cell score (SCS), a trait highly correlated to mastitis incidence, and various production-related traits, including milk yield, protein yield, fat yield, and lactation persistency. While no significant associations were found between these SNPs and SCS, SNPs in IL10 receptor beta subunit showed a significant effect on protein yield and lactation persistency. While there is evidence that IL10 plays an important role during lactation, it is also likely that the effects of SNPs in IL10 receptor beta subunit on protein yield and lactation persistency are due to linkage disequilibrium with a neighboring QTL. Copyright © 2011 Taylor and Francis Group, LLC.