San Francisco coach Kyle Shanahan will seek revenge for the 49ers' drubbing in last year's playoffs at the hands of the reigning Super Bowl champion Seahawks as the NFC West foes clash in Seattle Sunday.
Also in a packed NFL gameweek, the Packers and Bears take their historic rivalry back to Green Bay, high-flying Jacksonville face Philadelphia in London, and the Los Angeles Rams host the Buffalo Bills in a tantalizing test of this season's two current Super Bowl favorites on Monday.
San Francisco were thumped 41-6 back in January's NFC divisional round playoff by Seattle, who went on to win the Super Bowl at the 49ers' own stadium.
Shanahan admitted his side, who have started this season a perfect 4-0, have extra motivation ahead of Sunday's rematch.
"Playing a divisional game always feels a little bit more, playing a big rival like the Seahawks always does, them being the Super Bowl winners, how the last game went, so everything," said the coach.
Shanahan served as a television analyst for the Super Bowl but admitted he left the stadium early, finding it "tough" to watch Seattle's dominant showing as a neutral.
But "I feel like we're a new team, they're a new team, and we'll see how this series starts this year. We've got them at least twice, and you never know if we have to play them a third," he added.
San Francisco quarterback Brock Purdy has been on scintillating form, galvanizing an ageing 49ers roster that is undefeated despite grappling with a seemingly never-ending injury crisis.
Deebo Samuel Sr, who rejoined the 49ers in August, has made the most of the opportunities provided by the absence of fellow receivers.
"You put the ball in Deebo's hand, and he can execute it. He runs as good as anyone," said Shanahan.
By contrast Seattle, after its 12-game winning streak was snapped, has looked shaky in recent weeks.
The Seahawks lost to a Washington Commanders team shorn of its star quarterback, before nearly allowing the winless Los Angeles Chargers back into last weekend's clash.
- 'Adversity' -
Elsewhere, Chicago travel to Green Bay having won three games this season each with different quarterbacks. With Caleb Williams still injured, backup Tyson Bagent should start.
One of the NFL's fiercest rivalries has been fueled in recent years by the animosity between head coaches Ben Johnson and Matt LaFleur.
The Bears' Johnson famously riled his opposite number by joking that he "enjoyed beating Matt LaFleur twice a year," while LaFleur may need to win back some fans after a 2-2 start by beating their old foes.
The Jaguars enter as favorites for this season's second game at London's Tottenham Hotspur Stadium, part of the NFL's ever-growing international schedule.
Jacksonville continue to go under the radar despite winning 11 of their last 12 regular season games.
Philadelphia are still reeling from the sudden retirement of stalwart offensive tackle Lane Johnson earlier this week, while star running back Saquon Barkley is doubtful with an injured hamstring.
"We're on a two-game losing streak... It's crazy but every adversity that I've been in through my life, they're not comfortable at the time, but they produce the most growth," said coach Nick Sirianni.
On Monday night, Los Angeles' SoFi Stadium will host a clash between the two teams most favored by bookmakers to win this season's championship.
After a flying start, Bills quarterback Josh Allen was culpable for a late interception on second down in their loss to the New England Patriots when a field goal would have forced overtime.
Buffalo will try to get back on track against a Rams side that entered the season to substantial hype and improved from an underwhelming start with a hard-earned win at Philadelphia last week.
Puka Nacua's return has boosted a Rams side targeting a Super Bowl that will take place at their stadium in February.
K.Smeets--LCdB