Proteas extended their lead over England to 300 runs as they reached 197-7 at lunch in their second innings on the third day of the first test at Centurion Park, looking to set an imposing target for the tourists.
Quinton de Kock bludgeoned 30 runs off 17 balls and is expected to try to continue the fireworks in the second session, along with Vernon Philander not out on five.
De Kock hit Jofra Archer for three sixes, the first two off just the second and third ball of his knock, in a clear signal of intent as the hosts looked to bat England out of the contest, albeit with two and a half days still left to play.
Test debutant Rassie van der Dussen, who made 51, and nightwatchman Anrich Nortje, eventually out for 40, combined for a 91-run fifth wicket partnership after South Africa had begun the day on 72-4 with a 175-run lead.
With 15 wickets falling on Friday, and overcast conditions on Saturday suggesting the possibility of even livelier bowling, England took a frustrating 90 minutes before finally achieving a breakthrough when Van der Dussen was trapped leg before wicket by Archer.
Nortje followed soon after, caught by substitute fielder Zak Crawley at shortleg off Archer, who had four wickets but conceded 83 runs in 13 overs. Van der Dussen and Nortje, who had batted at No. 11 in the first innings but in no way looked like a tailender, survived two reviews, several run out chances and some hostile bowling with Nortje taking a nasty blow to the ribs.
Van der Dussen’s half century came off 65 balls as he made a case for inclusion in the team for the rest of the four-match series after being selected for Centurion as the replacement for injured Temba Bavuma.
Dwaine Pretorius then went cheaply for seven after driving at Ben Stokes and being caught at first slip by Dom Sibley.
England began the day on the back foot when wicket keeper Jos Buttler went down with flu-like symptoms and sat out the session, with Jonny Bairstow taking the gloves.
Captain Joe Root went off with a similar affliction but returned to the field some 40 minutes before lunch, only to then go off again just before the break.
England have been ravaged by a flu bug since arriving in South Africa two weeks ago with no end to the outbreak in sight with three squad members still bedridden at their team hotel.
South Africa scored 284 in their first innings, to which England replied with 181.