A highly spread polymorphism flanking the 3. Calpha1 human IG heavy chain gene was identified. This polymorphism allowed the detection of an internal duplication within the 3' flanking region of both Calpha1 and Calpha2. This region has a regulatory function with four enhancer structures also present at the 3' end of the human Calpha2 as well as in that of mouse and rat single Calpha genes. The 5682-bp sequence of clone lambdapl8 described here starts 3' of Calpha1 and presents three open reading frames; one of them contains part of the tandem repeats with the 20-bp consensus described previously that is expressed in a poly(A)+ RNA and found in three dbEST clones of the human tonsillar cDNA library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this transcript is associated with polysomes. We also discuss the possibility of the presence of a new regulatory gene that does not encode an immunoglobulin and maps in the human IG heavy chain gene cluster.