Negative-strand RNA viruses have been refractory to genetic manipulation using recombinant DNA techniques. Recently, new techniques were developed that allowed the rescue of synthetic RNA molecules into influenza A viruses and, subsequently, into other negative-strand RNA viruses. These techniques are presently being used to study the molecular biology of these viruses. Questions concerning cis- and trans-acting elements that are involved in transcription and replication of negative-sense RNA viral genomes can now be addressed with reverse genetic approaches. Further development of this methodology has enabled the construction--by recombinant DNA techniques--of influenza A viruses that contain altered genomes. The phenotypic characteristics and possible applications of these novel transfectant viruses are also discussed.