More than 42 million Italians are being called to the polls on Sunday and Monday to elect 14 of the country's 20 regional governments, as well as some provincial and municipal councils.
Q: How significant is this?
Although Italians are focused on the Pope, the vote is seen as a key test for next year's general election.
It is also the first major electoral test since Romano Prodi, the former European Commission President, returned from Brussels last year to head the centre-left opposition coalition.
Both Prime Minister Silvio Berlusconi and Mr Prodi have played a prominent role in the campaign.
The former centre-left Prime Minister, Massimo D'Alema, resigned after a poor showing at the last regional elections in 2000.
This paved the way for Mr Berlusconi's victory at the general elections a year later.
Mr Berlusconi's centre-right ruling coalition has lost every major mid-term election - European, by-election, regional and local - since storming to power in 2001.
Q: What are the main regions to watch?
The Rome region of Lazio and the Milan region of Lombardy, two of Italy's main centres of power. There was much controversy over candidacies in both cases.
In Lazio there was a political scandal involving a far-right group founded and led by Alessandra Mussolini, grand-daughter of Italy's former Fascist ruler Benito Mussolini.
The Social Alternative group was initially banned from taking part in the poll over the alleged faking of signatures supporting Ms Mussolini, who went on a hunger strike.
It was later re-admitted by Italy's top administrative court, triggering heated protests by the incumbent regional president, the right-wing Francesco Storace.
Analysts say that while Ms Mussolini cannot actually win the Rome region elections, she could split the right-wing vote and take away enough votes from the incumbent to deliver victory to the centre-left candidate.
Q: What about Lombardy?
This is Italy's richest region and a key centre-right constituency. The incumbent, Roberto Formigoni, won a landslide victory last time round.
But the ruling coalition has since lost Milan Province and Mr Formigoni has said that if they were to lose the regional government too, this would herald the opposition's victory in next year's national elections.
There were misgivings about the incumbent's candidacy, because the Milan-based coalition partner, the Northern League, wanted to field its own candidate.
The Northern League accused Mr Formigoni of wanting to replace Mr Berlusconi as prime minister.
Q: What powers do regional governments have?
Their powers are growing. Regional presidents - also known as "governors" - are in control of regional budgets, particularly in wealthy regions.
Unlike the prime minister and the Italian president, they are directly elected by the people - something which, especially in the biggest regions, gives them political clout.
The national parliament is also debating a devolution bill, which would give regional governments exclusive law-making powers in health, education and local policing.
Q: What is the regional balance of power?
The centre-right controls eight of the 14 regional governments up for election, the centre-left opposition six.
Any confirmation or consolidation of this trend would be seen as a major victory for the ruling coalition. The opposite would boost opposition chances ahead of next year's general elections.
First results are expected after polls close on Monday afternoon.
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