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Born in Dudleyville, Alabama , Pepper graduated from the University of Alabama and Harvard Law School. After completing his LL.B. in 1924, Pepper spent a year teaching law at the University of Arkansas, and then moved to Perry, Florida, where he opened a law practice. He was elected to the Florida state house in 1929 for a single term, and unsuccessfully ran for the United States Senate in 1934, losing to Park Trammell. However, he won his second Senate bid just two years later, in a 1936 special election following the death of Senator Duncan Fletcher .

In the Senate, Pepper became a close ally of President Franklin D. Roosevelt, supporting the New DealAlternate meaning: New Deal (UK The New Deal was President Franklin D. Roosevelt's legislative agenda for rescuing the United States from the Great Depression. It was widely believed that the depression was caused by the inherent instability of the market and the Lend-Lease Act. He was re-elected in 1938Events January -June January 3 The March of Dimes is established by Franklin Delano Roosevelt. January 11 Frances Moulton is the first woman to become president of a US national bank. January 20 Wedding of king Farouk I of Egypt and Farida Zulficar in Cai and 1944Events World War II January January 4 The Battle of Monte Cassino begins. January 5 Murder of Danish playwright Kaj Munck January 17 British forces, in Italy, cross the Garigliano River. January 20 The Royal Air Force drops 2,300 tons of bombs on Berlin;, but lost his bid for a third full term in 1950Events January January 5 US Senator Estes Kefauver introduces a resolution calling for examination of organized crime in the USA January 6 The United Kingdom recognizes the People's Republic of China. The Republic of China severs diplomatic relations with by a margin of over 60,000 votes. The race was marked by echoes of the Red ScareThe term Red Scare has been applied to two distinct periods of intense anti-Communism in United States history: firstly from 1917 to 1920 and secondly in the early 1950s. Both periods were characterized by widespread fears of Communist influence on U.: rival George A. SmathersGeorge Armistead Smathers (born November 14, 1913) is an American lawyer and politician who represented Florida in the United States Senate for eighteen years. Smathers was born in Atlantic City, New Jersey (his uncle, William Howell Smathers, was a U. repeatedly attacked Pepper for having communist sympathies, pointing out his pro- civil rights platform and campaign for universal health care. It is also widely claimed that Smathers won the election by using linguistic tricks to attack Pepper before uneducated audiences, such as stating that Pepper had a "thespian" sister and a "Homo sapiens" brother, although Smathers repeatedly denied these claims during his term in the Senate.

Pepper returned to his law practice in Miami and Washington until 1962, when he was elected to the United States House of Representatives. He remained there until his death in 1989. In his House career, he is best known for strengthening the Medicare and Social Security programs.

A number of places in Florida are named for Pepper, including the Claude Pepper Center at Florida State University (housing a think tank devoted to aging) and the Claude Pepper Federal Building in Miami, as well as several public schools.