Gene frequencies at ten blood group loci, one serum protein locus, and four milk protein loci were determined for the Holstein-Friesian breed in the United States. The sample consisted of 8630 cows in 51 herds from 10 states. Because of the close linkage among casein subloci and the concimitant rarity of crossover-recombinant groups, casein gene combination or haplotype frequencies were determined also. As one means of comparison of systems, indices of homozygosity and number of effective alleles were calculated. These indices were proposed also to be useful tools for monitoring changes in genetic variability of breeds. Genotypes within codominant systems and phenotypes associated with paired-system combinations generally were not randomly occurring. Paired system phenotypes within the sire sample corresponded much more closely to expectations of randomness.