The association between apolipoprotein E phenotype and the presence of 2 electrophoretic populations of very low density (VLDL) lipoproteins from human sera, double pre-beta(VLDL)lipoproteinemia (DPBL), was studied in 2 groups of subjects, one from Italy and one from Finland. In both populations the prevalence of DPBL was significantly higher in subjects with E4/4 and E4/3 phenotypes than in the other phenotypes not containing the E4 isoprotein. This finding suggests that the presence of a structural variant of the apo E protein, the isoprotein E4, may be causally related to the appearance of DPBL phenomenon.