DON ISAAC ABRAVANEL and his family arrived in Castile as fugitives from justice. João II, king of Portugal, suspected that Don Isaac was implicated in an effort to displace the Avis dynasty from the Portuguese monarchy in favour of the house of Braganza. The family's flight may be said to have closed a circle in their life, for they had apparently left Seville for Portugal after the persecutions of 1391 and the conversion of the head of the family, Samuel Abravanel, who took the name of Juan Sánchez de Sevilla. The story of the family's flight from Portugal is interesting in its own right, but here we are concerned with its activities in Castile after its return, apparently as early as 1483. It re-established itself in that kingdom and adapted well to the new conditions. Francisco Cantera has indicated the route taken by these refugees, headed by Don Isaac: they crossed the border from Portugal to Castile and settled first in Segura de León (today Segura de la Orden) on the lands of the order of Santiago. There were many Jewish communities in this region, especially concentrations of those who had been expelled from Andalusia, whence they were driven by an order of the Inquisition dated 1 January 1483. Segura is 30 km. from the Portuguese border and close to both Lisbon and Évora in one direction, to Badajoz, Mérida, Cáceres, Plasencia, and other places with Jewish communities in the other. The family settled first in the region of Plasencia, where Isaac's brothers Yose and Jacob apparently remained until the expulsion.

The Catholic Monarchs first met Don Isaac in March 1484 in Tarazona. Don Isaac was joined by his nephew and son-in-law Yose, the mayordomo of the Duke of Viseu. We do not know who recommended the contact between the Crown and the Abravanel family. Doubtless the Crown realized that Don Isaac's experience of finance could further its ends. Menachem Dorman surmises that Abraham Senior brought Don Isaac Abravanel to the royal court and introduced him to tax-farming. Moreover, it should be noted that this contact took place despite the anti-Jewish restrictions imposed in their full severity during the early 1480s, after the order segregating Jewish neighbourhoods: the Jewish badge, the expulsion from Andalusia, and so on.