In 1721, the first form of immunisation through inoculation, called "engrafting", as well as variolation, was imported from Turkey thanks to Mary Mortagu, residing in Constantinople. As ambassador’s wife, she observed its widespread practice. Tissot wrote about it in his Avis au peuple sur sa santé and in the Compendio storico del metodo nuovo d’inoculare il vajuolo. Si descrive come si stabili’ in Inghilterra, quali fossero i suoi grandi effetti, e si dimostra, ch’e’ incontrastabilmente dovuto al Signor Sutton. Opera del Signor Povver  (Historical account of the new method of variolation. It describes how it was established in England, its major side effects and it proves that it is indisputably due to Mr Sutton. Work by Mr Power) … published in Venice in 1770 and held in the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova. It deals with inoculation of human pus, which provided a milder form of the disease and produced immunity. The procedure was not without risk, in fact, it was probably responsible for some epidemics, so its use was controversial and not immediate.

An example of a detractor is found in the work Lettera sopra il vajuolo spontaneo, e sopra i mali effetti dell’inoculazione of 1782 (digital copy), in which the anonymous author, identified as Germano Azzoguidi, dissuades the Venetian noblewoman Caterina Albergati from inoculating her daughter. Among the arguments, the doctor noted that the success rate of the treatment was not sure: it was lower in later trails than earlier ones, on a suspicion that "those early observations were made for the sake of the system that see only what it is looking for and imagining" (p. LXIII).

The first region in Italy to carry out variolation was Tuscany in 1756, when six children in the Hospital of Santa Maria degli Innocenti were inoculated, followed by the Republic of Venice in 1767. Details can be found in the publications held in the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova (digital copy of Relazioni d'innesti di vaiuolo fatti in Firenze nell'autunno dell'anno 1756. Distese dal dottore Giovanni Targioni Tozzetti. In Firenze: appresso Andrea Bonducci, 1757 and digital copy of Terminazione degl'illustrissimi ed eccellentissimi signori sopra provveditori e provveditori alla sanita. [Venice]: printed by li figliuoli del qu. Z. Antonio Pinelli,1768). The reports from 1768 to the health supervisors in Venice provide details of "the successful experiment in the Pio Spedale de' Mendicanti, first case of an inoculation in Venice by sovereign command", so that variolation be extended to the mainland according to the Senate decree "in accordance with the methods used in this Republic" (p. III).

... to the discovery of the vaccine