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This article attempts to reconstruct the different stages in the Neapolitan discussions about the inoculation of variola and the Jennerian vaccination. The contribution of A. Genovesi, F. Galiani and D. Cotugno, and the arrival in Naples of A. Gatti in the seventies, were decisive for these developments. If the inoculation was somewhat delayed, compared with other parts of Italy in which it had previously been successful, the case was different for the vaccination, which was accepted and rapidly encouraged by the Bourbon government. In the mid-eighteenth century, Naples became the model for "a correct politics of vaccination all over Europe".