Brother of Serafino. Ordained priest in 1860, he was professor of theology at the Vatican Seminary; then he entered the diplomatic service and in 1865 was sent as auditor to the internunciature in the Netherlands, moving the following year to Brussels in the same capacity. Called to Rome as substitute in the Secretariat of State (1875), he was an effective collaborator of Cardinals Antonelli and Simeoni and remained in that office until the beginning of the pontificate of Leo XIII, when (1878) he became auditor of the Roman Rota. Elected in 1880 titular archbishop of Sardi and apostolic delegate to Constantinople, he earned merit by composing the schism among the Armenian Catholics, who refused obedience to the legitimate patriarch Hansun. Appointed (1883) apostolic internuncio to Brazil, he was sent by Leo XIII as his representative to the coronation of Tsar Alexander III and in Russia negotiated the execution of the convention established between the Holy See and the Russian government regarding the appointment of bishops and instruction in seminaries. Upon his return from this mission, Leo XIII transferred him to the nunciature in Lisbon, where he successfully handled the question of royal patronage.
Cardinal in 1891, during his more than forty years as cardinal he held some of the most important offices in the Roman Curia: he was prefect of the Economy of the Congregation for the Propagation of the Faith (1892), prefect of the Congregation of the Council (1902), and master of the papal household (1914). He also carried out important missions abroad: papal legate at the consecration of the cathedral of Cork and at the Eucharistic Congresses of Brussels (1898), Metz (1907), London (1908), Cologne (1909), and Montreal (1910). He enriched the basilica of Saint Mary Major from 1897, opened and closed the Holy Door in the Jubilee years 1900 and 1925, and on 2 Apr. 1899 attended the first Mass of the young priest Eugenio Pacelli, celebrated at the altar of the Madonna “Salus Populi Romani” in the Borghese Chapel. Bishop of Palestrina from the consistory of 19 Apr. 1900, he became, upon the death of his brother Serafino, dean of the Sacred College and bishop of Ostia (6 Dec. 1915), and in the latter see he had the church of the Madonna “Regina Pacis” built. Favorable, during the course of his long life, to the resolution of the Roman Question, he had the joy of witnessing, a year before his death, the historic event of the Lateran Pacts.