Using an immunoblotting technique and goat antihuman C4, we observed five distinct electrophoretic variants of C4 in a panel of 60 random dogs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated C4 showed that dog C4 is composed of three polypeptide subunit chains (α, β, and γ) and that structural variability occurs within the α- and γ-chain regions. Two distinct molecular weight forms of both the C4α- (αA and αB) and C4γ-(γA and γB) chain were detected. The variant forms of C4α and C4γ were found in association with particular C4 allotypes.