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Brigitte Grothum was born in Dessau, Saxony-Anhalt, to an engineer and a teacher, and she was the niece of German aviation pioneer Hans Grade. Moving to Berlin at fifteen, she completed her matriculation at the Ricarda Huch School. Initially aspiring to be a pianist, a broken finger ended that dream. She then pursued acting lessons with Marlise Ludwig and Herma Clement, making her stage debut at nineteen at the Tempelhofer Zimmertheater. Since then, Grothum has maintained a near-continuous presence in various theaters, primarily in Berlin, but also in Frankfurt and Zurich. From 1987, she expanded her career into stage directing and producing, starting with her adaptation of Hugo von Hofmannsthal's Jedermann. In recognition of her contributions to theater, Grothum received the Order of Merit of the Federal Republic of Germany in 2000.
Beginning in 1955, Grothum starred early on as the lead in the equestrian wartime drama Das Mädchen Marion (1956). She played Grethe Weiser's daughter in the comedy Lemkes sel. Witwe (1957) and Elisabeth Bergner's daughter in the family saga Die glücklichen Jahre der Thorwalds (1962). Her major breakthrough came opposite Klaus Kinski, with whom she formed a lasting friendship, in the Edgar Wallace thriller The Strange Countess (1961). She appeared in two more Wallace adaptations: The Inn on the River (1962), again alongside Kinski as the dubious Gregor Gubanoff, and The Curse of the Yellow Snake (1963). On television, her roles include the Dürrenmatt adaptation Romulus der Große (1965), the three-part Francis Durbridge miniseries Ein Mann namens Harry Brent (1968), and guest appearances in popular crime series such as Tatort (1970), The Old Fox (1977), and Der Kriminalist (2006). She gained acclaim for her dual role as Magda Färber/Marion Mann in the long-running cult TV series Drei Damen vom Grill (1977), acting alongside Brigitte Mira and Harald Juhnke.
Alongside her extensive stage and screen work, Grothum has been a prolific voice-over artist since 1957, dubbing for actresses including Diana Rigg (in The Avengers, 1961), Lee Remick, Barbara Eden, Angie Dickinson, Diane Keaton, Carol Lynley, and Yvonne De Carlo.
Grothum has been married twice. Her second husband of fifty years was orthopedist Manfred Weigert, with whom she had two children: actress Debora Weigert and production manager Tobias Weigert.