Springboks duo Chiliboy Ralepelle and Bjorn Basson have both been suspended and sent home to South Africa after failing drugs tests.
Both players featured in Saturday's 29-25 victory against Wales before the South African Rugby Union was notified of the positive tests late on Sunday evening.
The players tested positive for a banned stimulant after their narrow 23-21 victory over Ireland the previous weekend.
Six Nations Rugby Ltd, which administers the November internationals, informed the South Africa of its findings and as a result the pair have been sent home from the Springboks' European tour.
Basson had already been ruled out of the remainder of the tour after suffering an ankle injury during the Millennium Stadium victory. The 23-year-old wing is the record holder for the most tries in a Currie Cup campaign.
24-year-old hooker Ralepelle has made 17 international appearances and was the first black player to captain the national side when he led them out against a World XV in Leicester.
Both players tested positive for methylhexaneamine, a "non-specified stimulant" on the prohibited substances list of the World Anti-Doping Agency (Wada).
Methylhexaneamine is scheduled to be reclassified as a "specified stimulant" from 1 January 2011.
The players have the right to request that their 'B' sample be tested.