Initially worked on by Giorgio Vasari between 1572 and 1574 and completed by Federigo Zuccari between 1575 and 1579, the painting had over the past four centuries become partially obscured by dust, candle smoke and in some places layers of darkened varnish.
Now for the first time in several hundred years, the work - a massive rendering of The Last Judgement - will once again be seen in all its glory.
Fine detail of textiles, jewellery and flowers are once again clearly visible, as are the colours of the 800 human and other figures featured in the work.
Before the conservation operation was carried out, most of the painting's colours were unknown - because they were so hidden beneath the dust and soot.
The past five years' work has allowed a fuller understanding of 16th-century Florentine art and architecture, say the conservators, led by art historian Cristina Acidini, deputy superintendent of the City of Florence's Artistic Heritage Department.
It is the first time that experts have been able to examine in such detail not only the art but also the architecture of the cupola of Florence's great Duomo. Most of the building was constructed
between 1296 and 1400, but the cupola (or dome) was completed only in 1436 after 16 years work.
The dome was the greatest masterpiece ever produced by one of the Renaissance's great architectural pioneers, Filippo Brunelleschi.
He may have been partially inspired by the great classical Roman domed temple, the Pantheon, which he is believed to have examined years earlier in the company of the artist Donatello.
The double-skinned dome is built of bricks - many of them pre-moulded
into special shapes, mainly for decoration. Vasari and Zuccari painted the great dome more than a century later under the patronage of the Medici rulers of Florence.
Painted in the initally complicated and finally plainer late Mannerist mode,
the work was excecuted at the time that this style was giving way to simpler Counter-Reformation artistic fashion.
Giorgio Vasari - who studied under Michelangelo - is perhaps most famous as the first great art historian. His book - Lives of the Most Excellent Italian
Architects, Painters and Sculptors - was first published in 1550 and is still in print today.
Federigo Zuccari was the key figure of the Roman Mannerist school - and when he was finishing the Florence dome painting he was arguably the most famous painter in Europe (after the death of Titian in 1576). Just prior to his work on the dome he worked briefly in England where he produced a portrait of Elizabeth I.
The operation to clean and conserve the Florence work has cost 3 billion lire - all provided by the Italian government - and has taken more than 175,000 man hours.
Work on conserving the painting started in early 1989 and was only completed this year, although it will not be unveiled to the public until Easter 1995.
Massive scaffolding had to be erected to carry out initial survey work and, subsequently, the conservation operation itself. The painstaking, back-breaking task had to be carried out up to 105 metres above the floor of the cathedral.
A 20-strong team had to develop a good head for heights - and Florence's artistic heritage department ensured that a dozen conservators were in operation at any one time.
Slightly different techniques had to be used on different surfaces. Some 25 per cent of the painting was created in fresco, while 65 per cent was executed in tempera. 10 per cent employed both techniques. The conservators also had to take account of other changes of painting technique between the two original artists. Giorgio Vasari appears to have painted only around 33 per cent of the work, while Federigo Zuccari produced the rest.
But soon this extraordinary masterpiece - the world's largest Renaissance painting - will be visible once again in all its beauty.
Indeed, because of modern lighting it will be the first time that the painted interior of Florence's dome has been seen in its full glory.
Even Zuccari and the Medicis never saw it as the public will see it next year.
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