This study was undertaken to determine the relationships between canine cellular and serological determinants and more recently described genes. Such relationships might reveal information about immunological reactivity or function of various proteins. To do this we studied the haplotypic associations of dog leukocyte antigen (DLA) class I and class II alleles determined from a panel of 14 DLA-D homozygous dogs. This panel of dogs was typed for the serological determinants DLA-A, DLA-B and DLA-C. Polymorphisms for DLA-DQA1, DLA-DQB1, DLA-DRB1 and DLA-88 were also determined. The number of alleles (one or two) for two microsatellite markers in the DLA region were also determined. Analyses of the nucleotide sequences and of the serological and cellular typing data revealed that phenotypic homozygosity, as defined by the DLA-D type in mixed leukocyte culture (MLC), tended to correlate with homozygosity at the DLA-DRB1 locus but not necessarily at the DLA-DQB1 locus. Furthermore, MLC specificity was determined by other loci besides DLA-DRB1 and DLA-DQB1. The amino acid at position 63 of the DR beta chain could contribute to the DLA-B serological specificity. DLA-88, the most polymorphic class I gene characterized to date, did not have an easily identifiable association with either the DLA-A or DLA-C class I serological specificities. Homozygosity or heterozygosity of each of two microsatellite markers, FH 2200 and FH 2202, located in the class I or class II region, respectively, did not correlate with homozygosity or heterozygosity of the most polymorphic known class I (DLA-88) or class II (DLA-DRB1) genes.