Abstract: The present invention provides non-human transgenic animals in which an antibody subtype is selectively inactivated such that the transgenic animals express a reduced level of IgG3 relative to the levels expressed by the corresponding wild-type animal. Selective inactivation is achieved by the disruption through homologous recombination of the a nucleic acid sequence which encodes a constant region in the antibody subtype. The present invention provides transgenic animals which contain a disrupted C.gamma.3 gene. These transgenic animals retain the ability to express other antibody isotypes and subtypes. The present invention further provides methods for using these transgenic animals for screening candidate therapeutic compounds and for producing monoclonal antibodies which contain reduced levels of IgG3.