CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging. A coding sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP correlated with CR1 expression among African Americans. Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro-->Arg substitution and epistatic effects of another polymorphic gene.