The sacking rids Mandela's cabinet of a rebellious and divisive figure who publicly criticized his conservative economic policies. It does not affect Winnie Mandela's standing in the African National Congress or her position as a member of parliament.
A somber Mandela told a news conference he was relieving his wife of her duties as deputy cabinet minister of arts, culture, science and technology.
"This decision has been taken both in the interests of good government and to ensure the highest standards of discipline among leading officers in the government of national unity," Mandela said.
"I hope this decision will help the former deputy minister to review her position and seek to improve on her own conduct in positions of responsibility."
Immediately after the news conference, an eight-line letter from Mandela was delivered to Winnie Mandela's office informing her of the decision. Her spokesman, Alan Reynolds, said he told her of the letter in a telephone call.
"I have decided to terminate your appointment ... with immediate effect," Mandela said in the letter. "Thank you for the services you rendered to the government so far."
Firing his wife marks the most dramatic act Mandela, 76, has performed since coming to office almost a year ago in South Africa's first all-race elections.
Winnie Mandela has defiantly criticized the government's approach to social reform, made an unauthorized trip abroad and split the ranks of the ANC Women's League.
The series of controversies came to a head this month when police raided her home and offices on allegations she used her cabinet post to secure government contracts for a construction company she wanted to take over.
No charges have been filed, and a court last week threw out the search warrants issued for the raids. Police returned seized materials but said the investigation would continue.
Mandela named a human rights lawyer, Brigitte Mabandla, to replace Winnie Mandela, but made no other changes.
Winnie Mandela, 60, is one of the ANC's most popular leaders, finishing fifth in voting for the national executive last December. Her name and popularity as a long-persecuted, high-profile militant, popular among poor blacks, gave her a far bigger role in the country's politics than her minor cabinet post signified.
By sacking her from the cabinet, Mandela appeased critics who accused him of failing to act strongly against transgressions by ANC members. He also signaled a political parting of ways between ANC militants demanding faster reforms to help poor blacks and his own go-slow approach toward remaking South Africa.
The Mandelas separated a year after Winnie Mandela was convicted of kidnapping in the abduction by her bodyguards of four youths. One was later found dead. She paid a fine.
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