To the difficulties caused by disaster, depopulation and maladministration there was added the danger of foreign invasion when war broke out in Europe between Francis I.
The 17th and 18th centuries, however, mark the worst period of depopulation in the more malarious parts of the Campagna, which seems to have begun in the 15th century, though we hear of malaria throughout the middle ages.
This tells a story of depopulation under Spanish rule, to which the abandoned terraces (andenes) on the mountain sides, once highly cultivated, bear testimony.
Disease and depopulation resulted from this policy and at the end of the 18th century the Legislative Assembly decided to reduce the area of the pools which then covered twice their present extent.
The depopulation of Spain dates certainly from the Moorish conquest, possibly from the earlier Visigothic invasion.
After a six months' siege Pisa surrendered on terms (9th October 1406), and, although it was not sacked, many of the citizens were exiled and others forced to live in Florence, a depopulation from which it never recovered.
The neighbourhood is now very unhealthy, and it may be presumed that the process of depopulation, caused by increasingly unhealthy conditions and diminishing sources of food supply, was gradual.