British and Irish Lions coach Warren Gatland admits concerns over Johnny Sexton's "durability" were decisive in his omission from the 37-man squad.
Sexton, 35, made the 2013 and 2017 tours but the Ireland captain has struggled to stay fit and missed Leinster's last game with concussion.
Gatland instead opted for Dan Biggar, Owen Farrell and Finn Russell.
"There's no doubt that that was one of the toughest decisions that we had to make," said Gatland.
"I've got a huge amount of respect for Johnny and his quality, but it's such a pivotal position for us and it's about sending a message to the 10s that we have selected that we have the confidence and belief in them to do a job."
Sexton, who has started five of the past six Lions Tests under Gatland, missed Ireland's Six Nations defeat by France in February because of a head knock and was forced off during Leinster's Champions Cup quarter-final win over Exeter Chiefs in April after undergoing a head injury assessment (HIA).
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The fly-half also sat out the Irish province's Rainbow Cup loss to Munster and the Champions Cup semi-final defeat by La Rochelle on Sunday.
"When we looked at where we were going in South Africa, probably the thing that kept coming back to us was Johnny's durability, and being able to put a string of matches together consecutively, and big matches," added Gatland, whose side begin preparations for the Test series in South Africa with a warm-up game against Japan at Murrayfield on 26 June.
"He has been rested on a number of occasions and unfortunately that's possibly what swayed it for us in terms of us not having the confidence that he can get through what's going to be a tough, physical tour."
Gatland included eight Ireland players in his squad: Tadhg Furlong, Tadhg Beirne, Robbie Henshaw, Bundee Aki, Conor Murray, Andrew Porter, Iain Henderson and Jack Conan.
Like Sexton, James Ryan was a notable omission, and while Gatland admitted he was "pretty unlucky", the New Zealander cited Leinster's defeat by La Rochelle while explaining his decision to leave out the 24-year-old lock.
"For us it was getting that balance right with our second row and back row options, and covering those in certain positions as well, players being able to play either second row or back row," explained the former Wales boss.
"James is unlucky. I thought we saw an example, for me, with Leinster against La Rochelle last weekend. The La Rochelle side probably reminded me of what we're going to have to face in South Africa.
"We're going to face big physical men and we saw that with how direct they were in terms of coming off nine.
"Probably in the last couple of years with Leinster in a couple of those big games, and I know they were really good against Exeter, we saw that weekend and we saw 12 months ago against Saracens where people have gone pretty hard at them physically up front and that challenge."
On the Ireland players who did make the squad, Gatland highlighted that an ability to bring both "physicality" and "attractive rugby" led to the inclusion of Connacht and Leinster centres Aki and Henshaw.
"I thought the combination of Bundee Aki and Robbie Henshaw was outstanding for Ireland against England," he explained.
"We've got to be able to have that balance between the physicality they bring and the ability for us to play rugby, and I think both those players have got that.
"They can mix it and are able to roll their sleeves up when it does get tough, but they also can roll their sleeves up and play some positive and very attractive rugby."