Summary Our aim was to determine whether heterogeneity ofthe IgE (Ce) gene could be demonstrated in patients with chronic urticaria (CU). We performed Southern blots on DNA extracted from peripheral blood leucocytes of 20 patients with CU and 20 normal controls. Using a human Ce gene probe containing four exons ofthe constant segment ofthe IgE heavy chain, we showed the presence of a restriction fragment length polymorphism of the Ce gene segment in four of 20 patients with CU. but in none of 20 normal subjects. Family studies of two propositi revealed the presence of this Ce gene polymorphism in other family members. Our data show that a proportion of patients with CU have a polymorphism ofthe constant segment ofthe Ce gene. Further studies of this polymorphic gene fragment indicated that it was derived from duplication ofthe 3rd and 4th exons of functional Ce gene and was very likely to be located close to this gene. It raises the possibility that polymorphism ofthe functional Ce gene may affect expression of this gene. This could possibly lead to dysfunctional IgE-receptor interaction with consequent alteration in mediator release.