A yeast artificial chromosome was constructed with a 220-kb insert of the human IgH locus. This insert contained in germline configuration the mu and delta constant regions, the intronic enhancer, all six functional J-h regions, the entire D complex, and the five most proximal variable gene segments. An HPRT mini-gene was included downstream of the constant regions to aid targeting. Line 2B had one copy of the YAC intergrate into the mouse genome and was one of 7 lines generated. Southern blotting confirmed that the YAC integrated without any recombination events occurring. (J:23827)