Genetic variation at various human apolipoprotein gene loci plays a vital role in modulating lipid metabolism. However, information regarding genetic variation at apolipoprotein loci is scanty, and the available data are largely restricted to Caucasian populations. Using recently developed isoelectric focusing-immunoblotting techniques, we have screened a large number of serum samples from Nigerian blacks to investigate structural variation at six apolipoprotein loci: A-I, A-II, A-IV, C-II, E, and H. With the exception of a single example of a putative APO A-I variant, the APO A-I and A-II loci were found to be monomorphic. Several new variants have been identified at the APO A-IV locus, which are apparently restricted to the black gene pool. By comparison with Caucasians, in whom APO C-II is invariant, four allelic variants have been identified in the Nigerians at the APO C-II structural locus. A common three-allele polymorphism has been observed for APO E, with a striking high frequency of the APO E*4 allele. In addition to three common alleles, the APO H locus is characterized by having an allele marker unique to blacks. The mean heterozygosity at these apolipoprotein loci is higher in Nigerian blacks as compared with the Caucasians.