Nick Clegg has ruled out ever joining a coalition government alongside Ukip, saying it had been "difficult enough" finding common ground with the Tories.
He also took a shot at the "anti-everything" Green Party as he sought to play down another dismal Liberal Democrat by-election performance.
In the worst known result for a governing party, the Lib Dems limped in fifth with just 349 votes in Rochester and Strood on Thursday.
That was only just more than a fifth of the votes cast for the Green candidate in the contest which saw Ukip take a second Commons seat from the Conservatives.
Seeking to explain the result, the Deputy Prime Minister told reporters at a monthly press conference: "There was a sharp drop in the support for all the three main Westminster parties.
"The parties that espoused the politics of grievance and blame and anti-everything did well.
"That is, in a sense, not new. We are in a phase of politics at the moment where giving people a reason to be against things is pretty popular but grappling with the dilemmas that reality throws at you is less popular.
"One of the very worst things that can happen to the SNP north of the border, or even the Greens, would be if they actually had to take the decisions that we, as the United Kingdom as as whole, face at a pretty tricky time for the British economy and a time when the country faces threats around the world.
"We are avowedly not a country that seeks to exploit people's fears but to address them by showing that by having Liberal Democrats around the cabinet table we can secure the recovery, finish the job that we still need to finish."
With Nigel Farage's eurosceptic outfit now hopeful of winning sufficient seats at the May 2015 general election to hold the balance of power at Westminster, he was asked whether he could envisage joining a power-sharing administration that included them.
Mr Clegg, who led the Lib Dems into coalition with David Cameron's Tories in 2010, was adamant it would not happen under him.
"I will never sit around a cabinet table with Nigel Farage, that's for sure," he said. "I should think the feeling is pretty mutual.
"He represents the politics of fear, the politics of blame, the politics of vilifying foreigners and the politics of economic self harm by pulling the drawbridge up.
"It's difficult enough to compromise with more mainstream Westminster parties I have discovered, but it can be done at a push.
"Compromising with a party that I think basically wants to turn the clock back to the 1950s, has a very regressive attitude towards women, has a very ambivalent attitude to put it mildly towards the NHS - I just don't think you can see the Liberal Democrats and Ukip in the same space."
He declined to give any similar declaration about the Scottish National Party, which is currently tipped to significantly increase its representation at Westminster at the expense of Labour.
Mr Clegg said he was "not going to go through an endless menu of options".
He said his party "clearly have got our work cut out" to defy the opinion polls in 2015 but would succeed "where we are strong on the ground".
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