The Bank of England is withdrawing 63 million £50 notes from circulation following a review of the note's ability to withstand fraud.
The note in question bears the portrait of the first bank governor, Sir John Houblon, who took office in 1694.
From April 30, only the £50 note which celebrates the 18th century business partnership of entrepreneur Matthew Boulton and engineer James Watt, who helped forge the Industrial Revolution, will hold legal tender status.
Victoria Cleland, head of notes division at the bank, said: "If you have any Houblon £50 notes, it's best to spend, deposit or exchange them before April 30."
Around 224 million £50 notes worth £11.2bn are in circulation in total.
The bank said that from May onwards, retailers were unlikely to accept the Houblon notes as payment, but most banks and building societies would still allow customers to deposit them into their accounts.
Barclays (LSE: BARC.L - news) , NatWest, Royal Bank of Scotland (LSE: RBS.L - news) (RBS), Ulster Bank and the Post Office have agreed to exchange the older-style £50 notes for both customers and non-customers up to the value of £200 until October 30.
The Boulton and Watt note, which was brought into circulation in November 2011, was the first introduced by the bank to feature a green "motion thread" to bolster the currency's defences against counterfeiters.
It has five windows featuring the pound symbol and the number 50, which move up and down when the note is tilted from side to side.
In December, the Bank announced that it planned to issue plastic banknotes for the first time from 2016, when a new £5 note featuring Sir Winston Churchill appears.
A £10 note featuring Jane Austen will follow around a year later and also be made from polymer, rather than the cotton paper currently used, aimed at improving durability.
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