British No 1 Kyle Edmund and defending champion Marin Cilic bowed out of the Fever-Tree Championships at Queen's Club on Thursday.
Edmund, the last remaining British singles hope, went down 6-3 7-5 to top seed Stefanos Tsitsipas in a match played over two days.
He was a set down and 3-3 in the second when rain caused the first-round match to be suspended on Wednesday evening.
Edmund gamely fended off six match points but Tsitsipas got lucky with the seventh, Hawk-Eye showing his backhand had just clipped the line to secure the win.
Greek youngster Tsitsipas returned to the court later in the afternoon to beat Frenchman Jeremy Chardy 4-6 7-6 (7-0) 7-6 (7-4) and secure his place in the quarter-finals.
The 20-year-old will face Canadian teenager Felix Auger Aliassime after the 18-year-old, who had earlier beaten former world No 3 Grigor Dimitrov in straight sets, defeated Australian Nick Kyrgios 6-7 (4-7) 7-6 (7-3) 7-5.
Defending champion Cilic failed to hit form and was sent tumbling out of the tournament in the second round.
The out-of-sorts Croatian lost in straight sets to Queen's Club debutant Diego Schwartzman.
Argentinian Schwartzman, 26, secured early breaks in both sets to wrap up a 6-4 6-4 victory, only his third career win on grass.
Second seed Kevin Anderson, who beat Britain's Cameron Norrie in round one, was sent packing in three sets by France's Gilles Simon.
The big-serving South African, last year's Wimbledon runner-up, has missed a chunk of the season through injury and it told as Simon ran out a 6-1 4-6 6-4 winner.
French qualifier Nicolas Mahut was given a warning after hitting a ball girl in the face with a stray serve during his second-round win over Stan Wawrinka.
Mahut, having just lost a service game, sent a practice serve back over the net, inadvertently hitting the young girl. She was reduced to tears and, after being comforted by Wawrinka, had to leave the court.
Mahut received a code violation for unsportsmanlike conduct from umpire Mohamed Lahyani, but he gathered himself quickly to win the match 3-6 7-5 7-6 (2) to set up an all-French quarter-final with Simon.
Milos Raonic will meet Feliciano Lopez in the quarter-finals after the 2016 Wimbledon finalist defeated Aljaz Bedene 6-3 7-6 (7-3).
'Lazy' Kyrgios scolds himself for playing FIFA until 3am
Nick Kyrgios launched an expletive-ridden rant at umpire Fergus Murphy during his first-round match.
The Australian defeated Roberto Carballes Baena 7-6 (7-4) 6-3 but lost his temper after he claimed the Spaniard double-faulted on set point in the first set.
Kyrgios said: "Bro you are taking the f****** p*** mate? The ball was this far out, no joke. No joke. What are you doing? It's so far long. What are you doing? Like, what are you actually doing up there? It was this far out. Bro, it's taking the p***. I refuse to play."
After Murphy issued a code violation for unsportsmanlike conduct, Kyrgios continued his outburst.
"It couldn't have been further out. What are you doing? Jesus. Was that not out, the second serve? It's a joke, man. It's a serious joke," he said. "Like, your hat looks ridiculous, also. It's not even sunny."
After winning the first set on a tie-break, Kyrgios was nearing victory when he hit a poor lob to gift Carballes Baena a point.
"So lazy, do something, so lazy you are," he muttered to himself. "You were playing FIFA until 3am, what do you expect?"