His favourite method in wall-painting was to lay in his compositions in fresco and finish them a secco with a mixture of yolk of egg and liquid varnish. This, says Vasari, was with the view of protecting the painting from damp; but in course of time the parts executed with this vehicle scaled away, so that the great secret he hoped to have discovered turned out a failure. In 1463 he furnished a cartoon of the Nativity, which was executed in tarsia by Giuliano de Maiano in the sacristy of the cathedral and still exists. From 1466 date the groups of four Evangelists and four Fathers of the Church in fresco, together with the Annunciation on an oblong panel, which still decorate the Portuguese chapel in the church of S. Miniato, and are given in error by Vasari to Pietro Pollaiuolo. A fresco of the risen Christ between angels inside a Holy Sepulchre in the chapel of the Rucellai family, also still existing, belongs to 1467.
In 1471 Alessio undertook important works for tile church of Sta Tiinità on the commission of Bongianni Gianfigliazzi. First, to paint an altar-piece of the Virgin and Child with six saints; this was finished in 1472: next, a series of frescoes from the Old Testament which was to be completed according to contract within five years, but actually remained on hand for fully sixteen. In 1497 the finished series, which contained many portraits of leading Florentine citizens, was valued at a thousand gold forms by a committee consisting of Cosimo Rosselli, Benozzo Gozzoli, Perugino and Filippino Lippi; only some defaced fragments of it now remain. Meanwhile Alessio had been much occupied with other technical pursuits and researches apart from painting. He was regarded by his contemporaries as the one craftsman who had rediscovered and fully understood the long disused art of mosaic, and was employed accordingly between 1481 and 1483 to repair the mosaics over the door of the church of S. Miniato, as well as several of those both within and without the baptistery of the cathedral.