1918 pandemic in humans
The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs; this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it is not certain in which direction the virus was transferred, some evidence suggests that, in this case, pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918, after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and swine suggests that the 1918 outbreak in humans followed a reassortment event within a mammal, the exact origin of the 1918 strain remains elusive.

1976 U.S. outbreak
On February 5, 1976, in the United States an army recruit at Fort Dix said he felt tired and weak. He died the next day and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced that the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1). It was detected only from January 19 to February 9 and did not spread beyond Fort Dix.

This new strain appeared to be closely related to the strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) spread simultaneously, also caused illness, and persisted until March. Alarmed public-health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for the disease.

The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof that the vaccine was the cause. There were reports of Guillain-Barré syndrome, a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although if a link exists is still not clear, this syndrome may be a rare side-effect of influenza vaccines.

Overall, there were 1098 cases of Guillain-Barré Syndrome (GBS) recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. There are about one to two cases of GBS per 100,000 people every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. The CDC states that most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations.

1988 zoonosis
In September 1988, a swine flu virus killed one woman and infected others. The only pathogen identified was an H1N1 strain of swine influenza virus. Influenza-like illness (ILI) was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since 1-3 health care personnel who had cared for the pregnant woman developed mild influenza-like illnesses, and antibody tests suggested that they had been infected with swine flu. However, there was no community outbreak.

1998 US outbreak in swine
In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found that this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid stains would later form six out of the eight viral gene segments in the 2009 flu outbreak.

2007 Philippine outbreak in swine
On August 20, 2007, the Department of Agriculture officers investigated the outbreak (epizootic) of swine flu in Nueva Ecija and Central Luzon, Philippines. The mortality rate is less than 10% for swine flu, unless there are complications like hog cholera. On July 27, 2007, the Philippine National Meat Inspection Service (NMIS) raised a hog cholera "red alert" warning over Metro Manila and 5 regions of Luzon after the disease spread to backyard pig farms in Bulacan and Pampanga, even if these tested negative for the swine flu virus.