It has been suggested that apolipoprotein E (apoE) is inherited at a single genetic locus with three common alleles designated E2, E3, and E4. The products of these three alleles are apoE2, apoE3, and apoE4. The apoE phenotypes of 74 normal subjects and 226 hyperlipoproteinaemic subjects were ascertained by gel isoelectrofocusing. Patients with type I, type IIa, type IIb, and type IV hyperlipoproteinaemia had an apoE phenotypic distribution which was similar to that of normal subjects, with 40.0 to 60.0% being homozygous for E3. In contrast, 75% of type III patients had an E2 phenotype and 25% were E2/3 heterozygotes. Among type V patients 31.4% had an E4 phenotype, and 42.9% were E4 heterozygotes. No type III patient and only 5.7% of type V patients had E3 phenotype. The results suggest that apoE2 and apoE4 are associated with two distinctly different dyslipoproteinaemias and that apoE has at least two different physiological functions.