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Argentina will mark their inaugural match in the new Rugby Championship by handing Juan Martin Hernandez a first Test start in three years.
The fly-half has not played a full international since June 2009 but is back in the Pumas' starting XV for the historic clash at DHL Newlands on Saturday.
Argentina coach Santiago Phelan has named the same line-up that won a warm-up contest with French side Stade Francais last weekend, with one exception.
The lone change is made at inside centre as Santiago Fernandez returns in place of Martin Rodriguez.
Prop Rodrigo Roncero is set to win his 50th cap in as he takes his place in a pack that should once again be the Pumas' main asset in their attempt to be a competitive newcomer to the expanded competition, which was formerly known as the Tri-Nations.
"A lot of hard work has gone into ensuring we produce a good game and I believe playing against the three best teams in the world will help us improve," Phelan said.
"We are very excited and happy. Argentina have waited for this opportunity for a very long time and the six Tests we play during the next eight weeks are so important to us."
Springboks coach Heyneke Meyer has made a total of six changes to the team that drew with England in their last test in June.
Frans Steyn will win his 50th cap after being named at inside centre, while Andries Bekker and Lwazi Mvovo will start their first Tests of the year. No. 8 Keegan Daniel is handed a full debut after a finger injury to Pierre Spies.
"The Pumas have a great scrum, they are great maulers and I have noticed that their strength has improved, as well as fitness levels," Meyer said.
"Having watched a lot of footage of Argentina games and coached two players in the present squad while I was head coach of Leicester four years ago, I know how they play."
Hooker Bismarck du Plessis added: "It will be nice to have a different team to play against and new opponents to square up to," he said ahead of round 14 between the Springboks and the Pumas with the two-time world champions having won all the previous 13 Tests.
"There is a lot of respect between us and them and a healthy rivalry on the rugby field. South Africa helped develop Argentine rugby, so it is fitting that we play them first in the Championship."
South Africa: 15 Zane Kirchner, 14 Bryan Habana, 13 Jean de Villiers (c), 12 Frans Steyn, 11 Lwazi Mvovo, 10 Morne Steyn, 9 Francois Hougaard, 8 Keegan Daniel, 7 Willem Alberts, 6 Marcell Coetzee, 5 Andries Bekker, 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Bismarck du Plessis, 1 Tendai Mtawarira.
Replacements: 16 Adriaan Strauss, 17 Pat Cilliers, 18 Flip van der Merwe, 19 Jacques Potgieter, 20 Ruan Pienaar, 21 Pat Lambie, 22 JJ Engelbrecht.
Argentina: 15 Lucas Gonzalez Amorosino, 14 Gonzalo Camacho, 13 Marcelo Bosch, 12 Santiago Fernandez, 11 Horacio Agulla, 10 Juan Martin Hernandez, 9 Nicolas Vergallo, 8 Juan Martin Fernandez Lobbe (c), 7 Alvaro Galindo, 6 Julio Farias Cabello, 5 Patricio Albacete, 4 Manuel Carizza, 3 Juan Figallo, 2 Eusebio Guinazu, 1 Rodrigo Roncero.
Replacements: 16 Bruno Postiglioni, 17 Marcos Ayerza, 18 Juan Pablo Orlandi, 19 Tomas Leonardi, 20 Leonardo Senatore, 21 Martín Landajo, 22 Martin Rodriguez.
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