Former Liberal Democrat leader Lord Ashdown says the party's "trust" in David Cameron has been damaged as a result of the bitter alternative vote (AV) campaign.
Lord Ashdown insisted the coalition would stand the strain, but relations between the Lib Dems and Tories would be more "businesslike" in future.
He acknowledged it had been a "painful" night for the party, with voters believing they had been betrayed by leader Nick Clegg's decision to enter the coalition.
Lord Ashdown said Mr Cameron's refusal to distance himself from the No campaign's attacks on Mr Clegg ahead of the referendum "diminishes" the Lib Dems' view of the Prime Minister.
He told ITV's Daybreak: "The Prime Minister sets the tone of the politics for the nation. Mr Cameron had many, many occasions to dissociate himself from a campaign - by the way, funded by his party - whose primary purpose was personalised politics attacking his principal coalition partner and spreading scaremongering."
The conduct of the campaign, which together with the local elections provided the first major test of relations between the coalition parties, would fundamentally alter the nature of the administration, he predicted.
"It has been so far a relationship lubricated by collegiality, congeniality and trust. There will be less of that now. It's not less of a job to do, but the thing is going to be more businesslike, it's going to be more transactional. Who knows, it may be all the better for that."
Lord Ashdown said: "It's a painful night for us ... we acted in what we believed, and what I'm sure is right, is in the national interest to clear up the mess left behind by Labour. We believed, perhaps a little over-optimistically, that the British people would understand the difference between compromise and betrayal.
"But I think we have this morning to recognise with a little humility that there will be many who gave us their vote last year who don't see it that way and we are going to have to spend a bit more time to persuade them. This is not betrayal, it is acting in the national interest, it is making compromises - how else can you run a coalition?"
Lord Ashdown suggested the Tories' handling of the No to AV campaign had been "bloody stupid". He told Today: "If the Conservatives fund to a level of about 90% a No campaign whose primary task is to bring down their coalition partner, and then hand control of that over to the Labour war horses, and then stand back and say: 'Nothing to do with me guv' - I don't put that in the box marked betrayal but I put it in the box marked bloody stupidity."