The pope's subjects, but enclaved in the French realm, the inhabitants of Avignon and Venaissin are actually under the double protectorate of the pope and the French king. They thus benefit from a number of advantages. The former imposed neither direct taxes nor military fees; Francois I granted them the title of "regnicoles" (that is to say "inhabitants of the realm) and conceded certain commercial advantages. The economy prospered, based on tobacco, silkmaking, printing (in particular playing cards and counterfeiting) As well, the geographic and geopolitical situation favored the lucrative enterprise of contraband, much disgruntling the royal authorities.

This prosperity rested on a fragile base, subordinate to the political conjuncture, according to the condition of relations between king and pope. These relations were very good during the 16th century, but became strained in the rein of Louis XIV. Avignon and Venaissin served as hostages; they are occupied and temporarily united with the French kingdom in 1662 - 1663, 1688 - 1689 and 1768 - 1774. Economic pressure tightened, and in 1734, following a severe customs embargo, the fabrication of indiennes (fabric) was prohibited, and strict French protectionism measures severely punished the production by Avignon dyers in favor of neighboring French cities such as Nimes and Lyon. Governed by unpopular, feeble Italian vice-prelates, Avignon merchants and industrialist favorably considered integration into the kingdom, while the rural inhabitants of Venaissin remained profoundly attached to the pope's authority.