In dogs, high density lipoproteins (HDL) are the predominant plasma lipoprotein fraction (75-85%). This differs from humans where low-density lipoproteins (LDL) predominate. Because of the high HDL level of lipoproteins in dogs they have been considered to be atherosclerosis-resistant. Although dogs are considered to be atherosclerosis resistant reports have shown that atherosclerosis does exist in older dogs and in higher prevalence in some specific disease states. Recently in humans it has been shown that apolipoprotein E has several distinct allotypes which may be associated with distinct disease physiologic processes. Apolipoprotein E4 in humans associates with very low density lipoproteins (VLDL) while apolipoprotein E3 associates with HDL. In transgenic mice Apo E3 and Apo E4 associate equally with VLDL and intermediate density lipoproteins IDL. The Apo E3 and Apo E4 alleles both bind the LDL family of receptors with equal affinity. Of recent interest is the finding that ApoE4/ApoE4 associated with VLDL inhibits the anti-apoptosis effects of HDL and thus may yield some insight on possible mechanisms of the homozygous increased risk factor for atherosclerosis. The current study utilized 25 dogs representing 9 different pure breeds, and 3 mixed breeds, to survey the prevalence of apolipoprotein allele distribution in canids. Screening for the three common APOE alleles (E2, E3 and E4) was achieved using PCR-RFLP (polymerase chain reaction--restricted fragment length polymorphism) analysis exploiting the restriction enzymes Afl III and Hae II. These enzymes recognize the allele specific nucleotide substitutions at codons 112 and 158, respectively. Results showed that all dogs assessed by this methodology were homozygous for apolipoprotein E4 allele. It is possible that the finding of dogs being apolipoprotein E4 homozygous may be important in the pathophysiologic development of atherosclerosis in at risk disease populations or in furthering the understanding of cholesterol metabolism in dogs.