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Upon the death of wealthy Chicagoan Edward Dennis in the late 1920s, his nine-year-old son Patrick Dennis becomes the ward of their only living relative, Edward's equally-wealthy New-York-residing sister, Mame Dennis. Edward's will states that Patrick is to be raised Protestant in a "traditional" manner and that the trustee, Mr. Babcock of the Knickerbocker Bank, will pay Mame for expenses incurred in raising Patrick, but he has the right to refuse to pay if he deems that she's not honoring the spirit of Edward's will. Mr. Babcock and Patrick's longtime nanny, the timid Agnes Gooch, are to ensure that Patrick is raised correctly. Edward included these stipulations in his will knowing that his sister is a flamboyant, freewheeling, eccentric woman who can be considered anything but traditional or conventional. Despite the disruption each provides in the other's life, Mame and Patrick form a loving, supportive relationship. Mame wants to provide her sense of guidance to Patrick, which means exposing him to a broad spectrum of all that life has to offer. That changes when Mr. Babcock learns what is going on, and the stock market crashes resulting in Mame losing all her money, the events in combination leading to Mr. Babcock enrolling Patrick in boarding school to remove him from Mame's daily influence. Although not for herself, Mame realizes that she needs money to get Patrick back and support her entire family, which includes Agnes and her faithful butler Ito. She might get a little help from her best friend, Broadway actress Vera Charles, and a southerner she meets named Beauregard Jackson Pickett Burnside. Over the next several years, Mame's influence on those around her, including Patrick, is presented, although those relationships are not always smooth sailing, especially as Patrick grows into a man with his own mind.