England's match against South Africa on Saturday is the highlight of the first round of autumn internationals as the home nations start the build-up to next year's World Cup.
Coach Eddie Jones' men have won only one match in seven, and face a side who beat them in this summer's series and who went on to defeat New Zealand.
Scotland face Wales at the Principality Stadium - a match you can watch live on BBC One - and Ireland play Italy.
"It will be a proper Test on Saturday," said Wales coach Warren Gatland.
England v South Africa, Twickenham
|Venue: Twickenham Date: Saturday, 3 November Kick-off: 15:00 GMT|
|Coverage: Live commentary on BBC Radio 5 live, the BBC Sport website and app; watch highlights on BBC Two, BBC iPlayer and online from 19:30 GMT.|
England's strength-in-depth, or lack of it, will be put to the test on Saturday by the Springboks, who won the summer series between them 2-1.
Jones is without several England regulars, including Mako and Billy Vunipola, Chris Robshaw, Joe Launchbury and Courtney Lawes, who are all injured.
The Australian was counting on in-form back Manu Tuilagi being available, but the Leicester player was injured in training, freeing up a spot on the bench for Sale's Chris Ashton - back in the matchday squad for the first time in four years.
"Against South Africa you have got the physical battle up front and then you have to be tactically smart in how you attack against them," said Jones.
"We need to find ways to gain momentum, then once we find momentum, convert that to points."
England will have to contend with a strong Springbok pack. Their coach Rassie Erasmus said: "Jones knows our players and playing style. We've played [England] in June, it's only four or five months down the track. So we are used to one another, these two teams."
England face Rugby Championship winners New Zealand the following weekend, followed by World Cup hosts Japan on 17 November and Australia on 24 November.
Former England centre Jeremy Guscott: If they were to lose to all three of the southern hemisphere big beasts, but produce really good performances and lose with narrow points margins, then there is not masses to be concerned about.
England would be close to beating those sides, with another 10 months to fine-tune and close the gap before Japan 2019.
If England get hammered though and the performances are diabolical, there will be huge ramifications.
England will have gone backwards and that falls on Eddie and his team not doing a great job either coaching or selecting.
Wales v Scotland, Principality Stadium
|Venue: Principality Stadium, Cardiff Date: Saturday, 3 November Kick-off: 14:45 GMT|
|Coverage: Live on BBC One, S4C, BBC Radio Wales, Radio Cymru, the BBC Sport website and app.|
Scotland will be hoping to record their first win in Wales since 2002 when they meet in Cardiff on Saturday in the Doddie Weir Cup. The Welsh have also defeated their opponents in 14 of the past 16 meetings - home and away.
"As always we expect a very tough Test match against Wales in Cardiff - a contest that will be physically and technically demanding in a noisy arena," said Scotland coach Gregor Townsend, whose side lost 34-7 on their last trip to the stadium in the Six Nations in February.
Only four Scotland players retain their place from their win over Argentina in June, with fly-half Adam Hastings, son of former Scotland international Gavin, earning a third start.
Wales' Northampton fly-half Dan Biggar is unavailable this weekend as the game falls outside World Rugby's autumn Test window and coach Warren Gatland cannot pick players from the English Premiership.
Wales' record sevens try-scorer Luke Morgan will make his international XV-a-side debut, and is joined by seven returning British and Irish Lions, including centre Jonathan Davies following a 12-month injury absence.
"We are not going out there to play festival rugby. We want to play attractive rugby but smart and winning rugby," said Gatland.
"It is going to be tough, physical encounter."
Ireland v Italy, Soldier Field, Chicago
|Venue: Soldier Field, Chicago Date: Saturday, 3 November Time: 20:00 GMT|
|Coverage: Live text commentary on BBC Sport website.|
Six Nations champions Ireland will be revisiting Soldier Field in Chicago - the venue of their 2016 win over New Zealand - for their encounter over Six Nations rivals Italy.
Coach Joe Schmidt has rested several of his first-team regulars such as Johnny Sexton, Rory Best, Keith Earls and Peter O'Mahony before they embark on three matches in Dublin, including a contest against world champions the All Blacks on 17 November.
Only five members of the starting XV from Ireland's series win over Australia this year have been selected.
Munster's Joey Carbery gets a rare start at fly-half. Schmidt said: "His running game is a strength as is his work ethic, so that's always a good starting point."
And what about the world champions...?
New Zealand play Japan in Tokyo on Saturday before they face England, Ireland and then Italy on successive weekends.
Many of coach Steve Hansen's first-choice players have already headed to Europe to prepare for the forthcoming Tests, as he named a completely changed side from the one that defeated Australia last week.
Hansen said: "While this is a relatively inexperienced group, the expectation is that when you pull on the black jersey, then a top performance is required."
World Rugby Player of the Year nominees Beauden Barrett and Rieko Ioane are both rested for the Japan game but will feature in the matches in Europe.