Nicol Stephen has made the shock decision to quit as Scottish Lib Dem leader, saying the job was putting too much stress on his family life.
The former Scottish deputy first minister said his wife and four children had to take priority.
Mr Stephen, who was leader for three years, said he would stay on as MSP for Aberdeen South.
The party's deputy leader, Michael Moore MP, is to take charge while a leadership contest is staged.
Mr Stephen's immediate resignation came less than a week after Scottish Labour leader Wendy Alexander quit, amid an ongoing row over donations to her leadership campaign.
Party bosses will meet shortly to confirm a timetable to choose his successor, who is likely to be in place in September.
Possible contenders may include Shetland MSP and former transport minister Tavish Scott and the colourful backbencher Mike Rumbles, who previously challenged for the leadership.
Mr Stephen announces his resignation
The Scottish Liberal Democrats were ousted from power by the SNP last May, after serving in coalition rule with Labour for eight years.
But while the Scottish Labour leader at the time, Jack McConnell, later stood down, Mr Stephen stayed on to lead his party in opposition.
In a statement, he said it was time to put his four children, aged between four and 12, and his wife, Caris, first.
"Everyone involved in politics knows that there are stresses and strains on family life," Mr Stephen said.
"But when it goes beyond that, when it crosses a line, something has to be done.
"And at that stage - when you have to make a choice between family and politics - there can only be one answer.
"The health and wellbeing of your family has got to come first."
The responsibility of being a party leader, Mr Stephen said, had been even more demanding than those of being an MSP, adding: "You have to be available every day, every week.
"There is rarely a weekend, a birthday or a family holiday when the demands of the job do not intrude.
Mr Stephen served alongside Labour's Jack McConnell in coalition government
"That is not to complain - long hours and long absences from home go with the job.
"But it can all have an impact. And when that impact becomes too great, it is time to put my family first."
Mr Stephen's predecessor as leader, Lord Wallace, said he had done the "right thing".
"His determination, as party leader, to engage and involve young people and to build up the Party's support from the grassroots, will be a valuable legacy for his successor," added Lord Wallace.
Former Liberal Party leader and Scottish Parliament presiding officer Lord Steel said of Mr Stephen: "I wholly understand his decision. But I am equally certain that a man of his talent will return to the front line of politics in due course."
Under party rules, the post of Scottish Lib Dem leader must be filled by an MSP nominated by at least one other.
If there is more than one nominee, the winner will be decided by a ballot of party members.
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