Super 15 frontrunners ACT Brumbies take on the Queensland Reds and the Coastal Sharks go head to head with the Central Cheetahs on a weekend that could see the lead in all three conferences change hands.
Defending champions Waikato Chiefs, who lead the New Zealand conference, are away to the New South Wales Waratahs and must win to keep at arm's length the Auckland Blues, who automatically receive four points from a weekend bye.
The Brumbies' two-point lead over the Reds in the Australian conference will be under threat from the Queensland side, who enjoyed an accomplished 31-23 win over the Chiefs last weekend.
Jake White's Brumbies beat the 2011 champions 24-6 in the opening match of the Super Rugby season in Canberra, but Reds director of coaching Ewen McKenzie believes his team is much improved since that defeat.
"This is a game we've had on our minds since round one so it's good to be returning home and getting another crack at the Brumbies," McKenzie said.
"Our game has improved a lot since then and we also have the added benefit this week of continuity in our selections as there hasn't been the need to make a lot of changes."
The Reds' attack will be bolstered by the return of Wallabies winger Digby Ioane from a knee injury, with last week's two-try hero Rod Davies switched to the opposite wing.
Brumbies captain Ben Mowen has identified the back-row battle as key with veteran George Smith matching up against outstanding young Queensland flanker Liam Gill for the first time.
The Chiefs, two points ahead of the Blues in the New Zealand conference, have reacted to defeat against the Reds last week by making changes, with prop Pauliasi Manu and number eight Fritz Lee coming into the starting side and Brendon Leonard handed his first start at scrum-half this season.
"The Waratahs have one of the strongest teams in the competition on paper," Chiefs coach Dave Rennie said.
"They have been building well and will be a hell of a lot tougher at home. It is a big game for both teams coming off losses."
The Waratahs, coming off a bye after their loss to the Wellington Hurricanes, have Wallabies hooker Tatafu Polota-Nau and number eight Wycliff Palu back for Friday's clash in Sydney.
"When everyone is on song we're a pretty physical pack and I think we probably haven't been living up to our potential," Palu said.
"Hopefully this week is the week where we all switch on."
Coach Naka Drotske wants his Cheetahs players to improve their decision-making in Saturday's South African conference game against the Sharks in Durban.
"Our decision-making was left wanting against the Bulls (last week). That is one area that we cannot afford to come up short against the Sharks," he said.
Drotske has brought in Springbok prop Coenie Oosthuizen for the first time this season.
The Sharks lead the Cheetahs by three points in the South African conference and this will be their final match before a four-match tour of Australia and New Zealand.
John Plumtree's Sharks have been hit by injuries, with several of their key men -- Bismarck du Plessis (knee), Willem Alberts (shoulder) and Butch James (knee) -- missing.
The Bulls are unchanged for Saturday's derby with the Southern Kings in Port Elizabeth, while the Canterbury Crusaders have made three changes for Saturday's South Island derby with the Otago Highlanders.
In the weekend's remaining game, the Hurricanes take on Western Force in Wellington, while the Blues, Melbourne Rebels and Western Stormers have byes.