Gaylord M. "Greg" Focker (Ben Stiller) is a nurse living in Chicago. He intends to propose to his girlfriend Pam Byrnes (Teri Polo), a schoolteacher. His plans are disrupted by the news that Pam's sister Debbie (Nicole DeHuff) is getting married and Greg and Pam are invited to spend the weekend before the wedding at Pam's parents' house in Oyster Bay, New York (on Long Island). Hoping to make the best of the situation, Greg now plans to propose to Pam in front of her family and brings the engagement ring he bought for Pam with him.

At the Byrnes family home, Greg meets Pam's father Jack (Robert De Niro), mother Dina (Blythe Danner) and their beloved cat Mr. Jinx. Jack takes an instant dislike towards Greg and, subtly at first but more openly as time goes by, criticizes Greg for his choice of career as a male nurse and anything else he sees as a difference between Greg and the Byrnes family. Greg's surname remains a running gag throughout the film as characters frequently refer to Greg by his surname only. Greg desperately tries to impress Jack but his efforts fail one by one. Greg presents the family with a bottle of cheap champagne he purchased at a local drug store; while trying to open the bottle, the cork flies out of the bottle and hits the urn containing the ashes of Jack's beloved mother, breaking the urn and spilling the ashes on the ground, which Mr. Jinx then uses as a litter box, upsetting Jack even further.
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