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Orenthal James Simpson, also known by his nickname, The Juice, was originally best known as a stellar running back whose career included winning the 1968 Heisman Trophy, which he earned at USC, and a record-setting ten year tenure in the NFL with the Buffalo Bills and San Francisco 49ers.

In his second career, as an actor, O.J. himself entered the world of movie comedy, notably taking the role of Officer Nordberg, in the movie The Naked Gun: From the Files of Police Squad! and its two sequels. His acting, considered by some to be at best wooden, was actually not that bad, and he did set up a few genuinely funny moments.

Since 1994, though, his football stats and movie career have perhaps been overshadowed by his high-profile trial and subsequent acquittal of the charge of murdering wife Nicole Brown Simpson and friend Ronald Goldman. He was, however, later found liable for damages in a civil suit filed by Goldman's father and the Brown family.

According to a cut-away in Peter Griffin: Husband, Father...Brother?, a drunken Stewie planted suspicions in Simpson's mind which could have led him to a murderous attack on the two.

The famous "low speed pursuit", in which Simpson attempted to evade arrest by reportedly forcing fellow football player Al Cowlings to assist his escape, in a white Ford Bronco SUV, is parodied in Untitled Griffin Family History, where Nate Griffin and his family are shown escaping from the law, with the assistance of Al Cowlings and his trusty white bronco horse. The helicopter TV coverage of the Simpson/Cowlings pursuit is also referenced, as black versions of Tom Tucker and Diane Simmons report on the chase from a balloon.

In a No Meals on Wheels cut-away, Brian and his black room-mate react in entirely opposite ways (Brian in disbelief, the room-mate in pleasure) as the Simpson acquittal verdict is announced on TV, causing Brian to suggest, as they both point guns at each other, that maybe they should find new room-mates.

In Stewie Griffin: The Untold Story (and also Stu & Stewie's Excellent Adventure), the slogan on the Quahog Time Travel Vacations office is shown as "Watch O.J. Do It", a reference to the supposed murder.

At the very start of Love Thy Trophy, a teaser introduction on Quahog Channel 5 Action News claims, over pictures of O.J. playing golf and half removing his golfing glove, that evidence has been found to prove irrefutably that Simpson was innocent. No further details are given however.

In Long John Peter, Peter Griffin is shown emerging from the Brown-Simpson home, bloodstained, wearing one glove and carrying a bloodstained knife, just before O.J. arrives and enters, with the apparent intention of playing a game of Boggle. The former football player is then heard making a terrible discovery, presumably of two bodies, and speculating about what was going to happen, and what would now happen.

In The Juice Is Loose O.J. Simpson comes to live with the Griffins. He later murders three people in Quahog

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