Records on 7574 first lactation cows were used to investigate the associations between milk protein genetic variants and 305-day milk, fat, and protein yields. Friesians, Jerseys and Ayrshires and their crosses were represented in the data. Milk samples were typed for three casein (Cn) proteins alpha(s1)-Cn (B,C), beta-Cn (A(1), A(2)), kappa-Cn (A,B), and one whey protein beta-lactoglobulin (Lg) (A,B). The model used to describe the data included the additive genetic effect of animal and the four protein phenotypes. Hypotheses testing involved a test of the breed by protein phenotype interaction for each of the four milk proteins and, where appropriate, a test to determine whether the difference between the homozygotes was significantly (P<0.05) different from 0, as well as a test to determine whether the heterozygote was significantly different from the midpoint of the two homozygotes. The interaction between breed and beta-cn phenotype was significant for milk, fat and protein yields, while the interaction between breed and kappa-Cn phenotype was significant only for protein yield. The interaction associated with kappa-Cn was a scale effect, while the interactions associated with beta-Cn resulted from reranking of breed across the protein phenotypes. Across breed, alpha(s1)-Cn BC cows produced 1.9% less milk and 0.6% more protein than BE cows, while the differences between the phenotypes for fat production were small. The beta-cn A(2) allele was associated with increased production in the Friesians, with A(2)A(2) COWS producing approximately 2% more milk, fat and protein than A(1)A(1) cows. The opposite effect was found in Jerseys, where A(2)A(2) COWS produced 3-4% less milk, fat, and protein than A(1)A(1) cows. The B allele of kappa-Cn was associated with a 0.6-3.5% increase in production. The beta-Lg BE phenotypes produced approximately 1.3% less milk and protein and 1.2% more fat than the AA phenotypes.