Techniques of genetic engineering and expression have been applied to the production of antibodies in a variety of expression systems. Novel antibodies have been produced with a variety of modifications: as chimeric antibodies, as "humanized" antibodies, with catalytic groups, as bifunctional or fusion proteins, and as functional fragments such as Fabs or Fvs. The domain structure of the antibody is favorable to such manipulation; the novel proteins often retain their antibody-derived activity and acquire new properties as well. Chimeric and complementarity-determining region (CDR)-grafted antibodies have been effective in immunotherapy, but problems of immunogenicity remain. Combinatorial libraries produced in bacteriophage may present an alternative to animal immunization as a source of antigen-binding specificities. Structural and mutational analysis of variable regions is providing useful information about the requirements of the variable region for antigen binding. Careful analysis and comparison of effector functions among immunoglobulin isotypes may be applied to the design of effective therapeutic antibodies.