Abstract Immunoglobulin (Ig) genes are efficiently expressed following transfection into myeloma cells. The heavy and light chain genes, cloned into two compatible plasmids with different selectible markers, can be delivered simultaneously into the same cell. Rearranged variable regions genes of interest are isolated from hybridomas and joined to human and other Ig constant region genes or to non-Ig sequences to produce novel antibodies. Ig genes altered by exon shuffling or by site-directed in vitro mutagenesis provide genetically engineered antibodies that are potentially useful for studies of structure-function relationships, for immunological assays, and for diagnosis and therapy.