From medieval times, one word struck terror into the hearts of those who heard it: Plague! Infection with the plague was almost certainly a death sentence, with 60-80% of those who caught it dying.
The plague was nothing new. The first major epidemic was the Black Death in 1348-49. There were many outbreaks in Tudor times (most notably in 1563) and epidemics early in the Stuart period, in 1603 and 1625. But two things make the 1665 plague particularly notable. One was the sheer scale, with around 100,000 people dying in London (up to one-third of the total population). Second was the association with the Great Fire, which was wrongly assumed to have cleansed the city of the terrible disease.
The plague is commonly believed to have been carried by the fleas harboured by the city's black rats. These bred easily among the crowded, filthy streets. However, a recent theory suggests it may have been caused by a water-borne intestinal disease. Whatever the cause, the fire didn't get rid of it. The areas most affected by plague were the poor parishes to the east, north and south of the City. The Great Fire, on the other hand, destroyed areas within the City walls and by the river. Attempts to halt the spread of the plague became desperate. Entire families were locked inside their own houses if one of their number contracted the disease, with red crosses daubed on the doors. The alternative was to flee London, but this was often an option only for wealthy inhabitants – the King's court included. No-one knows for sure how many left, but it's believed that up to 15-20% abandoned the City.
One person who stayed in London throughout the 1665 plague was Samuel Pepys. Pepys' diaries offer a firsthand account of living through that awful year. He tells of coming across sick people and corpses, his horror at the sheer numbers of dead, and then how the toll started to decrease as the weather grew cold at the end of the year. Those treating the ill were clearly at great risk. One solution they employed was to wear heavy coats (which would have prevented fleas from biting them) and a beaked mask, stuffed with herbs and chemicals to ward off bad smells (miasma) and purify the air they breathed.
With so many dying, corpses were commonly buried in huge communal graves, known as plague pits. The locations of some are known, while rumours exist about others. Liverpool Street Station is said to stand on a plague pit. Another allegedly lies between Knightsbridge and South Kensington stations, causing the Piccadilly Line to sweep in a great curve to avoid it.
The plague never swept Britain so violently again. However, there were minor isolated outbreaks. And the continuing filth and lack of hygiene resulted in epidemics of other illnesses over the next few centuries - cholera in particular. These caused the deaths of thousands more Londoners until the sewers and London's rivers were finally cleaned up.