Prop Tendai Mtawarira has been forced to withdraw from South Africa's game against Ireland on Saturday after suffering heart palpitations.
Mtawarira suffered a recurrence of the ailment which has troubled him previously and was taken to hospital in Dublin although he was later released.
Former Leinster prop CJ van der Linde will replace Mtawarira at loose-head.
Current Leinster player Heinke van der Merwe has been called up to the replacements for the Dublin game.
It's not yet clear whether Mtawarira, who suffered the heart palpitations early on Saturday, will remain with the Springboks squad for the remainder of the current tour.
Van der Linde has played 73 times for the Springboks while Van der Merwe, who was called into the squad earlier this week, played in one previous Test in 2007.
Saturday's Aviva Stadium clash with see Ireland's South Africa-born hooker Richardt Strauss come face-to-face with his cousin Adriaan.
Uncapped Leinster front-rower Richardt has completed the required three years' residency and starts in the Irish front row alongside Leinster team-mates Cian Healy and Mike Ross.
Springboks vice-captain Adriaan Strauss will start at hooker, with Schalk Brits on the bench on his return to Test rugby.
Fly-half Pat Lambie, wing JP Pietersen and lock Juandre Kruger all start.
The changes are enforced because of injuries, with Johan Goosen, Bryan Habana and Andries Bekker unavailable among a string of absentees.
Ulster scrum-half Ruan Pienaar will start for the Springboks, as does Bath flanker Francois Louw.
Richardt Strauss, 26, joined Leinster as a 23-year-old after playing for the Cheetahs against the 2009 British and Irish Lions.
He has since played a major role in the Dublin province's last two Heineken Cup victories in 2011 and 2012.
Strong performances for his adopted country during the autumn internationals and Six Nations could put him in contention for a place on next year's Lions tour to Australia.
South Africa: Zane Kirchner, JP Pietersen, Jaco Taute, Jean de Villiers (capt), Francois Hougaard, Pat Lambie, Ruan Pienaar; CJ van der Linde, Adriaan Strauss, Jannie du Plessis, Eben Etzebeth, Juandre Kruger, Francois Louw, Willem Alberts, Duane Vermeulen.
Replacements: Schalk Brits, Heinke van der Merwe, Pat Cilliers, Flip van der Merwe, Marcell Coetzee, Morne Steyn, Juan de Jongh, Lwazi Mvovo.