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Harry Mathews was born in New York City in 1930. After attending Princeton University for two years, he joined the United States Navy in 1948. The next year, at age nineteen, he married the artist Niki de Saint Phalle. He completed a year in the navy before continuing his undergraduate studies at Harvard University, where he received a BA in music in 1952. He moved to Paris later that year to study conducting at the Êcole Normale de Musique, but after a short time, he dropped out and began his career as a writer.
In 1956 Mathews met the poet John Ashbery and became involved with the New York School. He and de Saint Phalle divorced in 1960, and in 1961 he cofounded the magazine Locus Solus with Ashbery, Kenneth Koch, and James Schuyler.
Mathews published his first novel, The Conversions (Random House), in 1962, and his first poetry collection, The Ring: Poems, 1956–69 (Juillard Editions), in 1970. He went in to publish several books of poetry, including The New Tourism (Sand Paper Press, 2010) and Armenian Papers: Poems 1954–1984 (Princeton University Press, 1987). He was also the author of numerous books of prose, including My Life in CIA: A Chronicle of 1973 (Dalkey Archive Press, 2005).
A highly experimental novelist and poet, Mathews was known for his idiosyncratic style and his frequent use of formal constraints. In 1973 he became the first American member of the French literary group OULIPO on the invitation of the writer Georges Perec.
In 1992 Mathews married Marie Chaix, a French novelist whose work he began translating in the 1970s. They divided their time among France, New York City, and Key West, Florida. Mathews died on January 25, 2017, in Key West.