Middlesex's unbeaten record in Division One this season is under threat after they were dismissed for 175 by Yorkshire at Lord's and forced to follow-on.
Seamers Steven Patterson and Liam Plunkett picked up four wickets apiece as the home side struggled after resuming day three on 16-1.
Joe Denly was the first to go as he was superbly caught at third slip by Joe Sayers off the bowling of Ryan Sidebottom, with skipper Chris Rogers following after a 25-minute rain delay when he fell to a diving catch to his left by Andrew Hodd.
Neil Dexter (11) and John Simpson (9) also fell cheaply as Middlesex slumped to 84-5, with Adam London falling victim to Plunkett (4-50) for 28 after he switched to around the wicket against the left-hander.
Plunkett then had Ollie Rayner trapped leg before, with James Harris going by the same mode of dismissal to Sidebottom.
The only real resistance came from Gareth Berg, who struck eight fours on his way to 54 before he too fell lbw as Patterson again caused problems.
Corey Collymore swiftly followed as Patterson (4-39) polished off the tail, to leave Middlesex trailing by 215 runs at the end of the first innings'.
The follow-on was duly enforced and Rogers, playing his last match for the county before joining up with Australia for the Ashes, fell to Sidebotton for a duck as the reply got off to a disastrous start.
Sam Robson and Denly attempted to hold things together and managed to put on 69 for the second wicket before spinner Adil Rashid came to the fore, Denly (31) stumped after being beaten by a well-flighted leg-break.
Robson also fell to the trickery of Rashid, bowled as he attempted to smash a short ball to the boundary.
There was still time for London to be trapped leg before to leave Rashid with figures of 3-51, the home side still 78 runs behind Yorkshire as they struggled to 137-4 at stumps.