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South Africa's pacemen routed Australia's batsmen with five late wickets to leave the hosts reeling at 111-5 at the close of day three.
Dismissed for 388 at tea to trail Australia's massive first innings total by 162 runs, Rory Kleinveldt took three wickets in a withering pace assault, with fellow quicks Dale Steyn and Morne Morkel taking a wicket each as the Adelaide Oval wicket bared its teeth late in the day.
First innings hero Michael Clarke and Mike Hussey survived a nervous few overs as shadows crept across the ground, with the hosts stuttering to a still-precarious 273-run lead.
Clarke, who scored a second consecutive double-century in the first innings, was on nine, with Hussey on five after a pulsating day in baking heat.
David Warner and Ed Cowan pushed the lead to 239, before Kleinveldt ended their 77-run opening stand amid a superb burst of swing bowling.
Kleinveldt, a late selection following a back injury to Vernon Philander, removed Warner for 41, the pugnacious opener miscuing a swipe off his pads to produce a simple catch to Du Plessis at extra cover.
The two-test paceman Kleinveldt then had Rob Quiney feathering an edge to wicketkeeper AB de Villiers in the same over, the Australian number three slumping to his second duck of the test following a nine in his sole innings in Brisbane.
Quiney made it a third in quick succession by bowling Cowan through the gate, before Dale Steyn had the out-of-form Ricky Ponting out for 16 when the former Australia captain played onto his stumps.
Nightwatchman Peter Siddle strode out to the crease to meet Clarke but headed back quickly, managing just one run, after nicking to De Villiers off Morkel.
The powerhouse display brought South Africa back into the match and the tourists will be mindful of history at Adelaide Oval, where the greatest successful run chase was by England in 1901/02 when they mowed down 315 for victory.
South Africa were earlier buoyed by fighting half-centuries from an injured Jacques Kallis and debutant Faf du Plessis before the tourists were dismissed at tea, still 162 runs short of Australia's massive first innings total of 550.
Kallis was courage personified as he smashed a fighting 58 despite a hamstring injury, anchoring a 93-run partnership with Du Plessis to guide the tourists past the follow-on.
Du Plessis also showed great composure with a 78 on debut and put the Australian attack to the sword with a breathless display of clean hitting in the final overs.
The pair had added a quickfire 70 runs before Australia captain Michael Clarke struck after the drinks break in the middle session, tempting Kallis into a miscued sweep.
With Kallis out for 58, spinner Nathan Lyon coaxed a similar shot from Morne Morkel minutes later and bowled the tall fast bowler middle-and-leg for six.
Du Plessis struck a defiant half-century on debut but was caught at silly mid-on by Clarke off Ben Hilfenhaus to bring the innings to a close.
All-rounder Du Plessis added a valuable 36 runs with spinner Imran Tahir, left stranded on 10 at the earlier than scheduled teabreak.
Siddle had earlier removed century-maker Graeme Smith and AB de Villiers in a fiery spell of 2-7 in the morning, after spinner Lyon had Jacques Rudolph caught.
Ben Hilfenhaus later took the new ball and had Dale Steyn out for one and Rory Kleinveldt for a duck.
It was offspinner Lyon who sparked the rout, however, as he coaxed Rudolph into an ill-conceived drive that went straight to Rob Quiney at cover.
With Rudolph out for 29, Smith was unable to dig in further as Siddle had him caught behind by Wade for 122.
The 31-year-old referred the decision but the video review was upheld and he trudged off the ground fuming.
Australia pace bowler James Pattinson left the field before the end of the first session to have treatment for a side strain.