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Henry Middleton (1717 – June 13, 1784) of South Carolina was the second President of the Continental Congress, and thus the leader of what was to become the United States, from October 22, 1774 until Peyton Randolph was able to resume his duties briefly beginning on May 10, 1775.

He was preceded in office by Peyton Randolph and was succeeded first by Peyton Randolph for a few days, then by John Hancock.

While a delegate to the Continental Congress, Middleton resigned in order to prepare for the coming war. He was succeeded by his son Arthur Middleton (1742-1787), who went on to sign the United States Declaration of Independence and the Articles of Confederation.

Arthur's son, also named Henry (1770-1846), had a long career in politics. He was Governor of South Carolina (1810-1812), U.S. Representative (1815-1819), and the Minister to Russia (1820-1830).

Several of Henry's other children married well:

• Mary Polly was married to Congressman Pierce Butler.
• Henrietta was married to Governor Edward Rutledge.
• Sarah was the first wife of Charles Cotesworth Pinckney. Charles Pinckney's brother Thomas Pinckney's son Thomas Pinckney Jr married Elizabeth Izard, a distant cousin of Congressman Ralph Izard. (Charles and Thomas Pinckney's sister Harriott was married to Daniel Horry, whose daughter married a son of South Carolina Governor John Rutledge. They were thus connected to the Grimke; Huger; Drayton; Laurens families of South Carolina and the Forten family of Philadelphia).
• Thomas married Anne Manigault. Their daughter Esther married Ralph Stead Izard, a distant cousin of South Caroina Congressman Ralph Izard and Alice De Lancey. (Alice was a niece of James DeLancey; James DeLancey's sister Susannah was the wife of Sir Peter Warren (Admiral). James DeLancey's daugther Anne was a wife of loyalist Thomas Jones (historian)}. Another daughter, Elizabeth Middleton, was married to Ralph DeLancey Izard, son of Congressman Ralph Izard.

(Note: Joseph, a brother of Anne Manigault, was first married to a daughter of Arthur Middleton and Mary Izard; by Joseph Manigault's second marriage he was the father of Confederate General Arthur Middleton Manigault (1824-1886), whose wife was a cousin 1st removed of Confederate General Benjamin Huger).

• Klos, Stanley L. (2004). Preisdent Who? Forgotten Founders. Pittsburgh, Pennsylvania: Evisum, Inc., 261. ISBN 0-9752627-5-0. 

• Middleton's Presidential Biography by Stanley L. Klos
• biographic sketch at U.S. Congress website
• Middleton Place