It has been demonstrated that the genetic polymorphism of human serum orosomucoid (ORM) is controlled by polymorphic ORM1 and monomorphic ORM2 loci. In this study a Japanese family was encountered in which several members had puzzling electrophoretic patterns consisting of four bands. The ORM patterns were due to the products of a duplicated ORM1 locus haplotype (ORM1 2.1) or the products of new variant alleles at the ORM2 locus. The ORM1 2.1 haplotype is very common in the Japanese population, occurring at an allele frequency of 0.16. The increased occurrence of ORM12-1 and the heterogeneity in band intensity among ORM12-1 phenotypes could be explained in terms of a duplicated gene ORM1 2.1. The ORM2 locus proved to be polymorphic, with six alleles in the Japanese population.