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"The frescoes that we are contemplating here introduce us into the world of the contents of the Revelation. The truths of our faith speak to us here from all sides. From them human genius took its inspiration undertaking to clothe them in forms of incomparable beauty" . With these words pronounced in the Homily during the Holy Mass celebrated on 8 April 1994, on the occasion of the completion of the restoration of the Last Judgement, the Holy Father John Paul II wished to place emphasis on the sacredness of the place in which the paintings, like the images of a book, serve to render the truths expressed in the Holy Scriptures more understandable.

The Sistine Chapel takes its name from Pope Sixtus IV della Rovere (pontiff from 1471 to 1484) who had the old Cappella Magna restored between 1477 and 1480. The 15th century decoration of the walls includes: the false drapes, the Stories of Moses (south and entrance walls) and of Christ (north and entrance walls) and the portraits of the Popes (north and south and entrance walls). It was executed by a team of painters made up initially of Pietro Perugino, Sandro Botticelli, Domenico Ghirlandaio and Cosimo Rosselli, assisted by their respective shops and by some closer assistants among whom Biagio di Antonio, Bartolomeo della Gatta and Luca Signorelli stand out. On the Ceiling Pier Matteo d'Amelia painted a starry sky. The work on the frescoes began in 1481 and was concluded in 1482. This is also the date of the following works in marble: the screen, the choir stalls (where the choristers took their places), and the pontifical coat of arms over the entrance door. On 15 August 1483, Sixtus IV consecrated the new chapel dedicating it to Our Lady of the Assumption. Julius II della Rovere (pontiff from 1503 to 1513), nephew of Sixtus IV, decided to partly alter the decoration, entrusting the work in 1508 to Michelangelo Buonarroti, who painted the Ceiling and, on the upper part of the walls, the lunettes. The work was finished in October 1512 and on the Feast of All Saints (1 November), Julius II inaugurated the Sistine Chapel with a solemn Mass. The nine central panels show the Stories of Genesis, from the Creation to the Fall of man, to the Flood and the subsequent rebirth of mankind with the family of Noah.

Reference to the first letter of Peter (3:20-22) is likely. In this the water of the flood is seen as a prophetic sign of the water of Baptism, from which a new mankind emerges, that of those saved by Christ. In the spaces between the webs we see, seated on monumental thrones, five Sibyls and seven Prophets. In the four corner pendentives are the Miraculous salvation of Israel while in the webs and lunettes (north and south and entrance walls) are the Ancestors of Christ. Towards the end of 1533 Clement VII de' Medici (pontiff from 1523 to 1534) gave Michelangelo the task of further altering the decoration of the Sistine Chapel by painting the Last Judgement on the altar wall. This caused the loss of the 15th century frescoes, that is to say of the altar-piece of the Virgin assumed among the Apostles and the first two episodes of the Stories of Moses and of Christ, painted by Perugino. In this fresco Michelangelo wished to show the glorious return of Christ in the light of the texts of the New Testament (cf. Matthew 24:30-31; 25:31-46; First letter to the Corinthians 15:51-55). The artist began the mighty work in 1536 during the pontificate of Paul III and completed it in the autumn of 1541. Using his extraordinary artistic capacities, Michelangelo tried to translate into visible forms the invisible beauty and majesty of God and guided by the words of Genesis he made the Sistine Chapel "the shrine of the theology of the human body".(Homily, pronounced by His Holiness John Paul II, 8 April 1994). The frescoes of the entrance wall were repainted in the second half of the 16th century: Hendrik van den Broeck repainted the Resurrection of Christ by Ghirlandaio, while Matteo da Lecce repainted the Discussion over the body of Moses by Signorelli, which had been seriously damaged when the door collapsed in 1522. The frescoes of the Sistine Chapel underwent a complete restoration between 1979 and 1999. The intervention also regarded the marble parts, that is the cantoria, the screen and the coat of arms of Sixtus IV. The Conclave for the election of the Supreme Pontiff is held in the Chapel. It is again the words of the Homily pronounced by His Holiness John Paul II that underline the primary importance of the Sistine Chapel in the life of the Church: "The Sistine Chapel is the place that, for each Pope, holds the memory of a special day in his life. ... Precisely here, in this sacred space, the Cardinals gather, awaiting the manifestation of the will of Christ with regard to the person of the Successor of St Peter [...]. And here, in a spirit of obedience to Christ and trusting in his Mother, I accepted the election that sprung from the Conclave, declaring [...] my readiness to serve the Church. Thus therefore the Sistine Chapel became once again before the whole Catholic Community the place of the action of the Holy Spirit that nominates the Bishops in the Church, and nominates especially he who must be the Bishop of Rome and the Successor of Peter".