This unit describes methods that can accurately determine the genotypes and phenotypes of human complement components C4A and C4B. Specifically, they allow investigators to determine how many C4 genes are present in a diploid genome of a human subject and to quantify how many of them encode C4A proteins and how many of them encode C4B proteins. In addition, methods to determine how many long and short C4 genes are present in a diploid genome of a subject are described together with experimental strategies to determine haplotypes and order or configuration of these genes in the MHC. Finally, methods to assess the degree of polymorphism in C4A and C4B proteins and whether low protein levels of plasma C4 may be caused by low C4 gene dosages and/or by mutant C4 genes.