Rabbit hemorrhagic disease (RHD), also known as viral hemorrhagic disease (VHD), is a highly infectious and lethal form of viral hepatitis that affects European rabbits. Some viral strains also affect hares and cottontail rabbits. Mortality rates generally range from 70 to 100 percent. The disease is caused by strains of rabbit hemorrhagic disease virus (RHDV), a lagovirus in the family Caliciviridae.

Rabbit hemorrhagic disease virus (RHDV) is a virus in the genus Lagovirus and the family Caliciviridae. It is a nonenveloped virus with a diameter around 35–40 nm, icosahedral symmetry, and a linear positive-sense RNA genome of 6.4–8.5 kb. RHDV causes a generalized infection in rabbits that is characterized by necrosis of the liver, disseminated intravascular coagulation, and rapid death. Division into serotypes has been defined by a lack of cross-neutralization using specific antisera. Rabbit lagoviruses also include related caliciviruses such as European brown hare syndrome virus.

RHDV appears to have evolved from a pre-existing avirulent rabbit calicivirus (RCV). Nonpathogenic rabbit caliciviruses related to, but distinct from RHDV, had been circulating, apparently harmlessly, in Europe, Australia, and New Zealand prior to the emergence of RHDV. In the course of its evolution, RHDV split into six distinct genotypes, all of which are highly pathogenic.

The three strains of rabbit hemorrhagic disease virus of medical significance are RHDV, RHDVa and RHDV2. RHDV (also referred to as RHDV, RHDV1, or as classical RHD) only affects adult European rabbits (Oryctolagus cuniculus). This virus was first reported in China in 1984, from which it spread to much of Asia, Europe, Australia, and elsewhere. A few isolated outbreaks of RHDV have occurred in the United States and Mexico, but they remained localized and were eradicated.

In 2010, a new lagovirus with a distinct antigenic profile was identified in France. The new virus, named rabbit hemorrhagic disease virus type 2 (abbreviated as RHDV2 or RHDVb), also caused RHD, but exhibited distinctive genetic, antigenic, and pathogenic features. Importantly, RHDV2 killed rabbits previously vaccinated with RHDV vaccines, and affected young European rabbits, as well as hares (Lepus spp.). All these features strongly suggest that the virus was not derived from RHDVa, but from some other unknown source. RHDV2 has since spread to the majority of Europe, as well as to Australia, Canada, and the United States.

Both viruses causing RHD are extremely contagious. Transmission occurs by direct contact with infected animals, carcasses, bodily fluids (urine, feces, respiratory secretions), and hair. Surviving rabbits may be contagious for up to 2 months. Contaminated fomites, such as clothing, food, cages, bedding, feeders, and water, also spread the virus. Flies, fleas, and mosquitoes can carry the virus between rabbits. Predators and scavengers can also spread the virus by shedding it in their feces. Caliciviruses are highly resistant in the environment, and can survive freezing for prolonged periods. The virus can persist in infected meat for months, and for prolonged periods in decomposing carcasses. Importation of rabbit meat may be a major contributor in the spread of the virus to new geographic regions.

RHD outbreaks tend to be seasonal in wild rabbit populations, where most adults have survived infection and are immune. As young kits grow up and stop nursing, they no longer receive the antibodies provided in their mother's milk and become susceptible to infection. Thus, RHD epizootics occur more often during the rabbits' breeding season.

Generally, high host specificity exists among lagoviruses. Classic RHDVa affects only European rabbits, a species native to Europe and from which the domestic rabbit is descended. The new variant RHDV2 affects European rabbits, as well, but also causes fatal RHD in various Lepus species, including Sardinian Cape hares (L. capensis mediterraneus), Italian hares (L. corsicanus), and mountain hares (L. timidus). Reports of RHD in Sylvilagus species have been coming from the current outbreak in the United States.