Using a specific monoclonal antibody (MB19) against human apolipoprotein B (apo B), we have detected a genetic polymorphism in human low density lipoprotein (LDL). MB19 bound to LDL from different individuals in one of three distinct patterns of immunoreactivity: strong, weak, and intermediate. Scatchard analysis revealed that LDLs with strong and with weak binding patterns differed 10-fold in their affinity for MB19, but both bound the same total amount of antibody (about one mole of MB19 per mole of apo B). LDL showing the intermediate binding pattern yielded a curvilinear Scatchard plot that could be resolved into two distinct components with affinities similar to those of LDLs exhibiting only the high- or only the low-affinity binding of MB19. LDL chemical composition was similar for all three MB19 binding patterns, and the polymorphism remained after removal of LDL lipid or carbohydrate. Analysis of plasmas from 77 unrelated individuals indicated that 40% of them bound MB19 with low affinity, 23% with high affinity, and 36% with intermediate or "hybrid" affinity. Family studies showed that the three MB19 binding patterns result from codominant transmission of two common apo B alleles, each coding for an allotype with different affinity for MB19, conditionally designated here MB19(1) (high affinity) and MB19(2) (low affinity).