For a short while he lived in Nikopol, but decided to make his way to the
Land of Israel so that he could immerse himself in
its sanctity and complete his written works. Passing through Salonica, he met the great
kabbalist Joseph Taitazak. He continued his journey to the Holy Land via Egypt and eventually settled in
Safed. At Safed, he met
Jacob Berab and was soon appointed a member of his rabbinical court. Berab exerted great influence upon him, and Karo became an enthusiastic supporter of Berab's plans for the reinstitution of
semikha "rabbinical ordination", which had been in abeyance for over 11 centuries. Karo was one of the first he ordained and after Berab's death, Karo tried to perpetuate the scheme by ordaining his pupil
Moshe Alshich. He finally gave up his endeavors, convinced that he could not overcome the opposition to ordination. Karo also established a
yeshiva where he taught
Torah to over 200 students. A
Yemenite Jewish traveler,
Zechariah Dhahiri, visited Rabbi Karo's
yeshiva in Safed and noted, When Jacob Berab died, Karo was regarded as his successor, and together with
Moses ben Joseph di Trani, he
headed the bet din of Safed. By this time, the
beth din of Safed had become the central bet din in all of
Old Yishuv (southern
Ottoman Syria) and of the
Jewish diaspora as well. Thus, there was not a single matter of national or global importance that did not come to the attention and ruling of the Safed bet din. Its rulings were accepted as final and conclusive, and sages from every corner of the diaspora sought Karo's halachic decisions and clarifications. Karo was also visited in Safed by the great Egyptian scholars of his day,
David ben Solomon ibn Abi Zimra and
Yaakov de Castro. He came to be regarded as the leader of the entire generation. in Safed In a dramatic testimonial,
Solomon Alkabetz testified that in Salonica, Karo had become one of the rare individuals who merited to be instructed by a
maggid—a private preacher who revealed to him many
kabbalistic teachings. The maggid exhorted Karo to sanctify and purify himself, and he revealed events that would take place in the future. In the "Gates of Holiness" (),
Hayyim ben Joseph Vital explains that visitation by a maggid is a form of
divine inspiration. The teachings of the maggid are recorded in his published work titled
Maggid Mesharim "Teacher of Righteousness".
Chaim Yosef David Azulai notes that only about one-fiftieth of the manuscript was published. However, in numerous places in the
Maggid Meisharim it states, "I am the Mishna that speaks in your mouth," indicating that the
Oral Torah itself (of which the
Mishna is the fundamental part) spoke within him. The Maggid promised him that he would have the merit of settling in the Land of Israel, and this promise was fulfilled. Another promise, that he would merit to die a
martyr's death like
Solomon Molcho had merited, did not transpire. His reputation during the last thirty years of his life was greater than that of almost any other rabbi since
Maimonides. The Italian Jew
Azariah dei Rossi, though his views differed widely from Karo's, collected money among the wealthy Italian Jews to have a work of Karo's printed and
Moses Isserles compelled the recognition of one of Karo's decisions at
Kraków. However, he had questions on the ruling. When some members of the community of
Carpentras in the
Kingdom of France believed themselves to have been unjustly treated by the majority in a matter relating to taxes, they appealed to Karo, whose letter was sufficient to restore to them their rights In the east, Karo's authority was, if possible, even greater. His name heads the decree of
herem (censure) directed against Daud,
Joseph Nasi's agent, and it was Karo who commissioned
Elisha Gallico to draw up a decree to be distributed among all Jews ordering that Azariah dei Rossi's "Light of the Eyes" (''Me'or 'Enayim'') be burned. Since Karo died before it was ready for him to sign, the decree was not promulgated, and the rabbis of Mantua contented themselves with forbidding the reading of the work by Jews under twenty-five years of age. Several funeral orations delivered on that occasion and some elegies from Karo's passing have been preserved. ==Published works==