The objective of this study was to investigate genotype by environment interactions for culling rates and milk production in large and small dairy herds in 3 US regions, using genotypes, pedigree, and phenotypes. Single nucleotide polymorphism (SNP) marker variances were also estimated in these different environments. Culling rates including cow mortality were based on 6 Dairy Herd Improvement termination codes reported by dairy producers. Separate data sets for culling rates and 305-d milk yield were created for large and small dairy herds in the US regions of the Southeast (SE), Southwest (SW), and Northeast (NE) for the first 3 lactation cows that calved between 1999 and 2008. Genomic information from 42,503 SNP markers on 34,506 bulls was included in the analysis to predict genomic estimated breeding value (GEBV) of culling rates and 305-d milk yield with a single-step genomic BLUP using a bivariate threshold-linear model. Cow replacement rates in large SE and NE herds were higher. Heritability estimates of culling rates ranged from 0.03 to 0.11, but the differences were small between large and small herds and among the 3 US regions. Genetic correlations between culling rates and 305-d milk yield were medium to high for cows sold for poor production and reproduction problems. Correlations of GEBV for culling rates among the 3 US regions ranged from 0.34 to 0.92 and were lower between the SW and the other regions, especially in small herds. Correlations of GEBV between large and small herds ranged from 0.44 to 0.90 and were lower in the SW. These results indicate genotype by environment interactions of cow culling rate between the US regions and between large and small herds. Correlations of top 30 SNP marker effects for culling rates between 2 US regions ranged from 0.64 to 0.98 and were higher than those of more SNP marker effects except for a culling reason “sold for dairy purpose.” Those correlations between large and small herds ranged from 0.67 to 0.98. High correlations of top SNP marker effects on culling reasons between the US regions and between large and small herds suggest that major markers can be useful for selection in different environments. The SNP variance shown in a marker gene segment on chromosome 14 was strongly associated with milk production in large and small herds in the NE but not in the SE and SW. Marker genes on chromosome 14 also showed a strong association with cow culling rates due to poor production and mortality in large herds in the NE.