Pakistan again showed England how to play in their own conditions in the first Test at Lord's on Friday before suffering a blow when Babar Azam was ruled out of the remainder of this two-Test series with a wrist injury.
The tourists scored 300 runs in Friday's play, going from an overnight 50 for one to 350 for eight at stumps on the second day.
That left them already 166 runs ahead of England's meagre first-innings 184.
But several hours after stumps, Pakistan found out Babar would play no further part after being injured while top-scoring with 68 on Friday.
The 23-year-old batsman had to retire hurt after being struck on the wrist by pace bowling all-rounder Ben Stokes.
Babar was taken to a hospital for a scan which confirmed he would not be able to get back on the field at Lord's or indeed take part in next week's second Test at Headingley.
"We took him for a precautionary X-ray which unfortunately confirmed a fractured left wrist," said Pakistan physiotherapist Cliff Deacon.
"It normally takes four to six weeks to heal so we will assess him with further X-rays."
The Pakistan Cricket Board added it had no intention to add a replacement batsman to the tour squad.
‘A 180-run lead would be ideal for Pakistan’ – Wasim Akram
Earlier, a quartet of Pakistan batsmen made fifties, with England dropping four catches on Friday and missing one other obvious chance.
Their had been hopes a return home would boost Joe Root's men following their recent series losses in Australia and New Zealand.
But after two days at the 'home of cricket', England were struggling to avoid a sixth defeat in eight Tests.
Experienced opener Azhar Ali laid the platform for Pakistan's reply with a well-made 50.
Asad Shafiq (59) and Babar kept the runs coming before Shadab Khan (52) hit his second half-century in three Tests.
Their efforts followed on from the disciplined and skilled bowling of Pakistan pacemen Mohammad Abbas and Hasan Ali, who took four wickets apiece on Thursday.
Pakistan coach Mickey Arthur, speaking before Babar was ruled out, praised his side's display but warned there was much still to be done if they were to go 1-0 up in the series.
"We've had two good days and we'll enjoy them, but we've got a hell of a lot of work still to do," he told Sky Sports.
"If we can get another 25 on top of that and do exactly what we did in the first innings – bowl in the right areas and apply some pressure – then we've got a really good chance."
Meanwhile, England paceman Mark Wood accepted Pakistan were on top, saying: "So far, they've out-bowled and out-batted us."
Pakistan resumed Friday with Azhar 18 not out and Haris Sohail 21 not out.
The second-wicket duo defended soundly and attacked when appropriate before Wood ended a partnership worth 75 runs when Haris (39) edged to wicket-keeper Jonny Bairstow.
Azhar completed a patient 133-ball fifty but was still on 50 when lbw to James Anderson, England's all-time leading Test wicket-taker.
Shafiq though hoisted debutant off-spinner Dominic Bess for six and Pakistan were 136 for three at lunch.
Alastair Cook, in his usual position of first slip, dropped Babar on 10 when he failed to hold a low chance.
Shafiq went to fifty and was then dropped on 59 by a diving Buttler in the gully.
But next ball Shafiq lobbed Stokes to Dawid Malan in the slips.
England took the new ball but Shadab and Faheem Ashraf kept the scoreboard ticking over in what was a first match at Lord's for both the young all-rounders.
Ashraf though was missed on 29 when he edged Wood between Bairstow and Cook for a catch that belonged to the keeper.
Shadab on 30 then presented Cook with a seemingly simple chance off Anderson only for the former skipper to put down the two-handed catch.
He completed a 62-ball fifty, including six fours, before a gloved hook off Stokes was well held by Bairstow in a rare England fielding highlight.