Five Saints players have been named in the England starting line-up to face a Sudamerica XV in Montevideo on Sunday (kick-off 19.30BST).
Tom Wood will captain the side with Luther Burrell and Stephen Myler being given their first starts for the senior side.
Ben Foden and Courtney Lawes will also be involved from the outset in the Uruguayan capital, while Lee Dickson and Paul Doran-Jones, who is still technically a Saint, are on the bench.
Prop Alex Corbisiero, who moves to Franklin’s Gardens from London Irish this summer, is also among the replacements.
And the Northampton players will now be looking to stake their claim for places in the squad for the Test matches against Argentina on June 8 and 15.
England head coach Stuart Lancaster said: “We have made a lot of changes from the Barbarians games as this tour is about giving players opportunities to show their talent. However the objective is to build on that performance and keep our game moving forward.
“The players understand this responsibility and are looking forward to the challenge.”
“Everyone involved will need to hit the ground running in Uruguay because we expect the Sudamerica side to play with a lot of skill and physicality in front of a passionate home crowd.
“It is England’s first ever match on Uruguayan soil and should be a great occasion for all concerned.”
England: Foden; May, Burrell, Eastmond, Strettle; Myler, Wigglesworth; Marler, Paice, Thomas; Lawes, Myall; Wood (c), Johnson, Vunipola.
Replacements: Buchanan, Corbisiero, Doran-Jones, Attwood, Kvesic, Dickson, Burns, Joseph.