Influenza A virus has been reconstructed entirely from cloned cDNA segments. Until now, the virus had been notoriously difficult to alter in vitro because the genome is distributed among eight subgenomic segments of negative-stranded RNA. Researchers have relied on the use of helper viruses to study the pathogen, but such approaches allow alteration of only a small subset of influenza virus genes. In the new work, published in Proc. Natl. Acad. Sci. USA (96, 9345–9350, 1999), scientists have transfected human cell lines with eight separate plasmids, each carrying the cDNA of a subgenomic segment in front of an RNA polymerase I promoter. The approach yielded highly concentrated virus stocks, and the cDNA plasmids were amenable to alteration by standard recombinant DNA techniques. Yoshihiro Kawaoka, a senior author on the paper, cautions that genetic engineering of influenza should be approached carefully: "Before initiating such experiments, scientists should weigh the risks and benefits of the studies and the containment levels at which the work should be performed." Historically, new strains of influenza have periodically caused deadly pandemics. Similar work by the teams of George Brownlee and Peter Palese will soon be published in the J. Virology ( 73, in press, 1999). Influenza induces strong mucosal immunity and does not integrate into the host genome, making it a potentially useful vector for both vaccines and gene therapy.