The Californian strain, which is endemic to the west coast of the United States and Baja in Mexico, is the most virulent, with reported case fatality rates approaching 100%.

Strains present in Europe and Australia were originally introduced from South America but have become attenuated, with reported case fatality rates of 50–95%.

Poxviruses are fairly stable in the environment and can be spread by contaminated objects such as water bottles, feeders, caging, or people's hands.

[15] A laboratory study in which European rabbits received intradermal injections of a South American strain of the myxoma virus demonstrated the following progression of disease.

Signs of the classic nodular form of the disease include a subcutaneous mass at the site of inoculation, swelling and edema of the eyelids and genitals, a milky or purulent ocular discharge, fever, lethargy, depression, and anorexia.

In rabbits infected with attenuated, less virulent strains of the virus, the lesions seen are more variable and generally milder, and the time course is delayed and prolonged.

Vaccinated rabbits often present with localized scabbed lesions, frequently on the bridge of the nose and around the eyes, or multiple cutaneous masses over the body.

A 1931 paper reported twelve cases of myxomatosis from Santa Barbara, Ventura, and San Diego counties of California.

[17] A 2024 study found that myxomatosis caused by the MSW strain (California/San Francisco 1950) of the myxoma virus occurs regularly in the greater San Jose and Santa Cruz regions of California.

Domesticated rabbits that spent time outdoors were at greater risk of acquiring the disease, and most of the cases occurred between August and October.

[20] Because the clinical signs of myxomatosis are distinctive and nearly pathognomonic, initial diagnosis is largely based on physical exam findings.

[21][22][23] If a rabbit dies without exhibiting the classic signs of myxomatosis, or if further confirmation is desired, a number of laboratory tests are available.

[13][19] Negative-stain electron microscopic examination can be used to identify the presence of a poxvirus, although it does not allow specific verification of virus species or variants.

Theoretically at least, a single viable virus present in a specimen can be grown in cultured cells, thus expanding it to produce enough material to permit further detailed characterization.

[13] In other countries where less virulent strains are present and vaccines against the disease are available, supportive care may help rabbits to survive the infection.

Cessation of food and water intake, ongoing severe weight loss, or rectal temperatures below 37 °C (98.6 °F) are reasons to consider euthanasia.

It is recommended that all rabbits in areas of the world where myxomatosis is endemic be routinely vaccinated, even if kept indoors, because of the ability of the virus to be carried inside by vectors or fomites.

[3] In Europe and the United Kingdom a bivalent vectored vaccine called Nobivac Myxo-RHD[28] is available that protects against both myxomatosis and rabbit haemorrhagic disease.

Poxviruses are stable in the environment and can be spread by fomites but are highly sensitive to chemical disinfection; bleach, ammonia, and alcohol can all be used to deactivate myxoma virus.

In November 1937, the Australian Council for Scientific and Industrial Research used Wardang Island to conduct its first field trials of myxomatosis, which established the methodology for the successful release of the myxoma virus throughout the country.

[40] In 1950, the SLS strain of myxoma virus from the South American tapeti (Sylvilagus brasiliensis) was released in Australia as a biological control agent against feral rabbits.

[41] In June 1952, Paul-Félix Armand-Delille, the owner of an estate in northwestern France, inoculated two wild rabbits with the Lausanne strain of myxoma virus.

[42] His intention was to only eradicate rabbits on his property and town, but the disease quickly spread through Western Europe, Ireland and the United Kingdom.

This in turn drove specialized rabbit predators, such as the Iberian lynx and the Spanish imperial eagle, to the brink of extinction.

[47] Two pairs of European rabbits set free in 1936 at Punta Santa Maria resulted in an infestation that spread over the northern half of Tierra del Fuego.

In 1954 Chilean authorities introduced a Brazilian strain of myxoma virus to Tierra del Fuego, which succeeded in bringing rabbits to very low population levels.

[48] Given the importance of viral evolution to disease emergence, pathogenesis, drug resistance, and vaccine efficacy, it has been well studied by theoreticians and experimentalists.

The introductions of myxoma virus into European rabbit populations in Australia and France created natural experiments in virulence evolution.

Both in modes of resistance and of virulence, and in all countries in which the virus has been introduced for control of feral rabbits, the hosts and the pathogens have continually adapted in various ways to evolutionary challenges.

For example, in spite of long-term concern in Australia especially, where the initial virulence of myxomatosis declined after a few decades in the field, rabbit evolution of resistance to the disease has not gone unchallenged.