Summary Until recently, development of vaccines against the various forms of human viral hepatitis involved different approaches; human viral hepatitis is caused by fundamentally different viruses, and each form and its associated disease have posed different problems, but recent advances in molecular biology, particularly in molecular cloning of DNA, have provided more uniform means of vaccine development. Viruses causing hepatitis A, B and delta (a defective virus) have been identified; the agents causing hepatitis non-A, non-B (probably at least two or three kinds) remain unknown. Vaccines against hepatitis A virus (HAV) and B virus (HBV) have been developed. HAV grown in cell cultures becomes attenuated after 10–20 serial passages, and such live attenuated virus vaccines are undergoing clinical trials. Preparation of inactivated HAV vaccines seems infeasible because only small amounts of antigen are produced in cell culture. For HBV, a different approach has been taken: safe and efficient HBV vaccines have been prepared from the surface antigen of HBV (HBsAg) naturally present in the plasma of HBsAg carriers, and these vaccines provide an immunity of at least 3–5 years in 80–90% of vaccinated individuals. Both these approaches to vaccine production are not so very different from the pioneer preparation of a rabies vaccine by Pasteur a hundred years ago, but the advent of recombinant DNA techniques has fundamentally changed vaccine production. The genome of HAV is being cloned and sequenced; preparation of polypeptides will shortly become possible, as well as the use of live hydrid viruses containing that part of the HAV genome which codes for the peptides responsible for inducing neutralizing antibodies. The DNA genome of HBV has been cloned and sequenced, and the genes coding for the proteins for HBsAg and the hepatitis B core antigen (HBcAg) have been localized. Prokaryotic (bacterial) and eukaryotic (yeast and mammalian) cells have been used to express these genes in vitro . HBV genomes have been inserted into vaccinia viruses and HBsAg polypeptides have been synthesized. The detailed characterization of these new forms of vaccines and their clinical efficiency are still under evaluation, but the prospects of controlling hepatitis A and B are better than before. No efforts have yet been made to develop vaccines against hepatitis delta, and vaccines to protect against hepatitis non-A, non-B must wait until these agents have been identified and characterized. When the time comes, though, vaccines against these forms of hepatitis will also be chemically synthesized or produced by recombinant DNA technology.