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The sanctuary was built between 1604 and 1609 over a small chapel having a fresco of the Madonna and Child from 1400s. The construction was due to a miraculous event. While in 1604 the painter Stefano Minicucci was restoring the painting, miraculously, blood came out. The next year they had collected sufficient funds to start a sanctuary of light Baroque style from drawings of Jacopo Barozzi da Vignola, with an octagonal dome that ends with a lantern.

In the forecourt of the sanctuary you can see the many shops that since the eighteenth century were created to meet the needs of pilgrims.

The choir loft and the organ were made in the seventeenth century by the French design architect Channequiau, who had designed the Notre Dame portals.

The Brotherhood, which had a substantial revenue, entrusted the work of construction of the organ to Parma Giulio Cesare Burzi March 16, 1635 for 550 scudi. The organ was then expanded in 1655 by maestro Giacomo Marchesi Aretino. This organ was then played by Handel in 1707 when, on a trip to Italy, he composed the sonata “Coelestis dum spirat aura” for the feast of St. Anthony of Padua of Vignanello on 13 June.

On June 18 of that year Handel obtained from the Farnese lords of Vallerano permission for a “Salve Regina”, in G minor for solo soprano, Margherita Durastanti, strings, concertante organ and basso continuo, in Madonna del Ruscello Church.