Ben Stokes bagged his first five-wicket haul since July 2018 but Durham face a battle to avoid a last-day defeat as Lancashire captain Keaton Jennings haunted his former employers once more.
Stokes opted out of next month's T20 World Cup to build up his bowling workloads in the Vitality County Championship and get back to being a fully-fledged all-rounder in England's Test programme this summer.
While he collected 5-98 from 20 overs of toil for a match analysis of 38-2-169-7, the England Test captain's efforts were overshadowed by Jennings' second century in this Division One clash.
Jennings, who played for Durham from 2012 to 2017, followed up his first-innings 115 with 155 second time around before falling to Stokes as Lancashire declared on 353-9, leaving a target of 475.
Durham closed on 134-3 and while the in-form David Bedingham is unbeaten on 31 and Stokes is still to bat, they need an unlikely 341 at Blackpool to deny Lancashire a first win of the season.
England opener Zak Crawley made a stunning double century to lead a stirring Kent fightback in their follow-on against Somerset at Taunton.
Having been dismissed for a golden duck the day before, Crawley thrashed 238 from just 267 deliveries, underpinning Kent's 409-5 and carrying them into a slender 33-run lead.
Defending county champions Surrey thrashed Worcestershire by 281 runs at the Kia Oval as Dan Worrall collected a 10-wicket match haul.
Worrall followed up a six-for in the first innings with 4-35 as Worcestershire were all out for 231, having been set an improbable 513 for victory following Jordan Clark's 98 and Dan Lawrence's 87.
An exciting finish is in store on Monday at Trent Bridge as Hampshire reached stumps on 84-5, still needing a further 85 to beat Nottinghamshire.
After Nottinghamshire were dismissed for 209 to leave their visitors 169 for victory, Hampshire slumped to 44-5 but Fletcha Middleton (33 not out) and James Fuller (23no) ensured no further losses.
Jordan Cox will resume on 77 not out from Essex's 224-4 as they chase a further 106 to beat Warwickshire at Chelmsford.
In Division Two, an Ollie Robinson-inspired Sussex claimed a 21-run win over Joe Root's Yorkshire at Hove.
Robinson, who came in for criticism during England's Test tour of India in the winter amid question marks once more over his fitness, claimed 4-42 including the wicket of Yorkshire dangerman Adam Lyth for 73 with a wicked bouncer.
Root was trapped lbw by Danny Lamb for 10 as Yorkshire fell short in their pursuit of 183, all out for 161.
Rishi Patel top-scored with 117 in Leicestershire's 371 but they were made to follow-on and closed 24-0 against Gloucestershire, still 311 short of making their opponents bat again at Grace Road.
Marnus Labuschagne (111) and Colin Ingram (105) helped Glamorgan to 293-6 against Middlesex and an advantage of 133 at Cardiff.
Emilio Gay's unbeaten 89 ushered Northamptonshire to 195-2 and into a 255-run lead against Derbyshire, who were earlier all out for 362 as Ben Sanderson claimed 5-76 at Derby.
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