The Mishnah on today’s daf (=page) lists a number of cities that had the unique status of arei homah – walled cities – with the special laws that applied to them (see, for example, yesterday’s daf). These are defined as cities that were surrounded by walls from the days of Joshua, and they include Zippori, Gush Halav, Yodfat, Hadid, Ono and Yerushalayim.
The Gemara quotes a baraita where Rabbi Yishma’el b’Rabbi Yossi explains that these cities were enumerated because they were recognized by the returning exiles at the beginning of the second Temple period and resanctified (for details on the sanctification ceremony, see Shevu’ot 16a). This is explained by the Gemara as necessary, since kedusha rishonah kidshah le-sha’atah ve-lo kidshah le-atid la-vo – the original sanctity of the land during the first Temple period was only established for that time, but not for the future. For this reason, only those cities that were resanctified by Ezra and the community that returned to Israel were granted the status of arei homah. The sanctity of these cities impacts on the laws of selling houses within them (which is the topic of discussion in our Gemara), but also grants them a higher status of holiness so that, for example, a metzorah – someone suffering from biblical leprosy – would not be permitted to remain in the city (see Mishnah Kelim 1:7).
The Rambam(Mishneh Torah, Hilkhot Shemittah Ve-Yovel 12:15-16) rules that this sanctity was removed with the destruction of the second Temple, and these cities will need to undergo a process of resanctification again when the third Temple is built. This stands in contrast with the sanctity of the city of Jerusalem, where the Rambam rules that even if the holiness of the Land is removed, kedushat Yerushalayim – which stems from the presence of God – can never be removed.