The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted to form a new virus.

The first record of the outbreak in Hong Kong appeared on 13 July 1968. By the end of July 1968, extensive outbreaks were reported in Vietnam and Singapore. Despite the fatality of the 1957 Asian Flu in China, little improvement had been made regarding the handling of such epidemics. The Times newspaper was actually the first source to sound alarm regarding this new possible pandemic.

By September 1968, the flu reached India, Philippines, northern Australia and Europe. That same month, the virus entered California from returning Vietnam War troops but did not become widespread in the US until December 1968. It would reach Japan, Africa and South America by 1969. The outbreak in Hong Kong, where density is about 500 people per acre, reached maximum intensity in 2 weeks, lasting 6 weeks in total from July to December 1968, however worldwide deaths from this virus peaked much later, in December 1968 and January 1969. By that time, public health warnings and virus descriptions were issued in the scientific and medical journals.

In comparison to other pandemics, the Hong Kong flu yielded a low death rate, with a case-fatality ratio below 0.5% making it a category 2 disease on the Pandemic Severity Index. The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population. In the United States, approximately 33,800 people died.

The same virus returned the following years: a year later, in late 1969 and early 1970, and in 1972. Fewer people died during this pandemic than the two previous pandemics for various reasons:

	Some immunity against the N2 flu virus may have been retained in populations struck by the Asian Flu strains which had been circulating since 1957
	The pandemic did not gain momentum until near the winter school holidays, thus limiting the infection spreading
	Improved medical care gave vital support to the very ill
	The availability of antibiotics that were more effective against secondary bacterial infections

The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N1 infections in the late 19th century. The virus was isolated in Queen Mary Hospital. In the 1968 pandemic vaccine became available one month after the outbreaks peaked in the US.

Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans.

The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian Flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics. However, cross-immunity within and between subtypes of influenza is poorly understood.