He returned to Sweden as a coach at the Royal Opera, Stockholm, and made a conducting debut there in 1940. In 1942 he made his debut as a concert conductor in Göteborg (Gothenburg), soon leading to his appointment as music director of the Stockholm Concert Society.
In 1953 he took the position of principal conductor and music director of the Stockholm Royal Opera. As such, he showed an interest in unusual repertory, and led productions of practically forgotten operas and bold new works, such as Blomdahl's Aniara, a science-fiction opera that was the first opera to include electronic music interludes. In 1954 he taught the course for conductors in the Salzburg Mozarteum. He retained his post at the Stockholm Royal Opera until 1960. Meanwhile, in 1963 he succeeded Paul Paray as music director of the Detroit Symphony Orchestra (through 1973). Beginning in that year he took a position teaching conducting at New York's Juilliard School and regularly conducting at the Metropolitan Opera. These associations lasted until 1987.
He was music director of the Göteborg Symphony Orchestra (1974-1976), musical adviser and principal guest conductor of the Denver Symphony Orchestra (1978-1985) and artistic adviser of the San Diego Symphony (1985-1988).