Nielsen's career began in dramatic roles on television during "Television's Golden Age", appearing in 46 live programs in 1950 alone. He said there "was very little gold, we only got $75 or $100 per show." He narrated documentaries and commercials and most of his early work as a dramatic actor was uneventful. Hal Erickson of Allmovie noted that "much of Nielsen's early work was undistinguished; he was merely a handsome leading man in an industry overstocked with handsome leading men." In 1956, he made his feature-film debut in the Michael Curtiz-directed musical film The Vagabond King. In the Seattle Post-Intelligencer, Nielsen remembered Curtiz as "a sadist, a charming sadist, but a sadist". Nielsen called this film "The Vagabond Turkey". Though the film was not a success, producer Nicholas Nayfack offered him an audition for the science-fiction film Forbidden Planet, resulting in Nielsen's taking a long contract with Metro-Goldwyn-Mayer (MGM).  Forbidden Planet became an instant success, and roles in other MGM films such as Ransom! (1956), The Opposite Sex (1956) and Hot Summer Night (1957) followed. In 1957 he won the lead role opposite Debbie Reynolds in the romantic comedy Tammy and the Bachelor, which, as a Chicago Tribune critic wrote in 1998, made people consider Nielsen a dramatic actor and handsome romantic lead. However, dissatisfied with the films he was offered, calling the studios "a Tiffany, which had forgotten how to make silver", Nielsen left MGM after auditioning for Messala in the 1959 Ben-Hur. Stephen Boyd got the role. After leaving the studios, Nielsen landed the lead role in the Disney miniseries The Swamp Fox, as American Revolutionary War hero Francis Marion. In a 1988 interview, he reflected on the series, saying, "That was a great experience, because the Disney people didn't do their shows like everyone else, knocking out an episode a week. ... We only had to do an episode a month, and the budgets were extremely high for TV at that time. We had location shooting rather than cheap studio backdrops, and very authentic costumes." Eight episodes were produced and aired between 1959 and 1961.  His television appearances include Justice, Alfred Hitchcock Presents, Voyage to the Bottom of the Sea, The Virginian, and The Wild Wild West. In 1961, he was the lead in a Los Angeles police drama called The New Breed. He guest-starred in a 1964 episode of Daniel Boone with Fess Parker in a minor but credited role. In 1968, he had a major role in the pilot for the police series Hawaii Five-O, and appeared in one of the seventh-season episodes. In 1969, he had the leading role as a police officer in The Bold Ones: The Protectors.  In 1972, Nielsen appeared as the ship's captain in The Poseidon Adventure. He also starred in the William Girdler's 1977 action film, Project: Kill. His last dramatic role before mainly comedy roles was the 1979 Canadian disaster film City on Fire, in which he played a corrupt mayor. In 1980, he guest-starred as Sinclair on the CBS miniseries The Chisholms.

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