Italian voters snubbed a weekend referendum on changes to the justice system, dealing a blow to Matteo Salvini, the leader of the rightist League party, who had championed the plebiscite.
Results released early Monday showed just 20.9% of people cast a ballot, the lowest ever for a referendum in Italy and well below the 50% threshold needed for the result to be valid.
The five questions related to a reform of Italy's notoriously inefficient judiciary, but critics said the issues were too technical for many voters.
"We have lost. It is pointless trying to deny it," said Roberto Calderoli, a League veteran and member of the Senate.
The national referendum was held alongside local votes for mayors in almost 1,000 towns and cities, testing the strength of parties ahead of next year's parliamentary elections.
The formal count does not begin until 2.00 p.m. (1200 GMT) but exit polls for the six major cities up for grabs showed centre-right groups leading four of the races and the centre-left ahead in two.
The centre-right looked on course to take charge of the northern port city of Genoa and the Sicilian capital Palermo straight from the first round of voting, while run-off ballots looked likely in the other big centres.
In a surprise, the centre-left was ahead in the northern city of Verona, traditionally a right-wing bastion, but where the conservatives failed to rally behind a joint candidate.
A total of 26 provincial and regional capitals were contested on Sunday, 18 of which are currently held by the centre-right bloc made up of the League, Brothers of Italy and Forza Italia, led by former prime minister Silvio Berlusconi.
The centre-left alliance of the Democratic Party (PD) and the 5-Star Movement will claim progress if it increases its tally of five cities, while the PD will be hoping to top Brothers of Italy as the party with most support.
Brothers of Italy, which is the only major party not to be part of Prime Minister Mario Draghi's broad unity government, took just 4% of the vote at the last national election in 2018, but is now running at around 22% in the polls.