Australia took four wickets in the evening session to leave South Africa with an improbable task of saving the second Test on day five tomorrow at the Adelaide Oval.
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The hosts set South Africa an intimidating total of 430 to win the Test thanks to some important knocks by the lower order and the Proteas lost four wickets before the close of play.
Captain Graeme Smith was dismissed on just his second ball and Hashim Amla and Alvaro Petersen were also heading back to the pavilion soon after.
Jacques Rudolph faced 34 balls, adding just three runs before he became the fourth casualty as Nathan Lyon took his second wicket of the innings.
The tourists ended the day on 77-4, with A B de Villiers and Faf du Plessis sticking it out with slow runrates in the middle.