Italy's Justice Minister Clemente Mastella has said he is stepping down after his wife was put under house arrest over a corruption scandal.
Mr Mastella wants to be "more free" personally and politically
"I am throwing in the towel," he told the Italian parliament.
His wife, Sandra Lonardo, who leads the council in Italy's Campania region, said she had done nothing wrong.
Mr Mastella said the inquiry was part of a witchhunt against him. It has emerged in a court document that he, too, is under investigation.
Prosecutors are looking into allegations of a corrupt hospital appointment at a state hospital in Caserta near Naples.
Neither Mr Mastella nor his party have commented on his own involvement in the inquiry.
Ms Lonardo said she had a "clear conscience" and was quoted as saying that her family was the victim of a campaign.
"I think this is the bitter price my husband and I are paying for our defence of Catholic values," she said.
Mr Mastella's party of Catholic Christian Democrats is a small but important part of Romano Prodi's centre-left government.
Its three seats in the Senate give the prime minister a wafer-thin majority in the upper house, and the party has said it will continue to support him.
In his resignation speech, Mr Mastella said "between the love of my family and power I choose the former".
He said he wanted to be "more free from a political and personal point of view".
In a statement, Prime Minister Prodi said he rejected his justice minister's resignation.
Mr Mastella had already threatened to resign over possible changes to Italy's electoral law.
The country's constitutional court gave the go-ahead on Wednesday for a referendum on raising the threshold for political parties to enter parliament.
Mr Mastella's party would be one of a number in the coalition which could lose out if the referendum went ahead.
The BBC's David Willey in Rome says that "what started as a small local scandal near Naples could end up forcing the government to resign".