Until his election to the see of Alexandria in 385, St [[Jerome]] noted that Theophilus had not shown himself as a public teacher. <ref>"Contra Rufin.", III, 18, in P.L., XXIII, 492</ref> In July 385, he was elected to the [[cathedra]] of Alexandria. About 391, having received permission from Emperor [[Theodosius the Great (emperor)|Theodosius]] to build a [[church]] on the site of the pagan temple to Dionysus, Theophilus provoked a confrontation with the pagans by mockingly displaying artifacts from the temple. During the confrontation, Theophilus caused the destruction of the temple to Serapis, <ref>Socrates Scholasticus, ‘‘The Ecclesiastical History’‘, 16</ref> over which he built a church.
During the early years of his episcopate in Alexandria, Theophilus maintained good relations with his fellow clergy. In 394, when he was in Constantinople for the first time for a council he sat with Nectarius of Constantinople, [[Gregory of Nyssa]], and Theodore of Mopsuestia. He got along well with [[Origen]] and his [[monasticism|monastic]] friends, the four [[monk]]s of Scetius, known as the “Tall brothers”. He included as members of ecclesiastical offices a number of the clergy of Alexandria. Among these was Isidore, whom he made an [[archpriest]] and patriarchal oeconomos. He supported the teachings of Origen in a number of disputes. He banished an opponent of Origen, Bishop Paulus, and reproached St. [[Jerome]] for showing hospitality to Paulus.
In 395, however, Theophilus abruptly changed his attitude, a change that apparently grew out of a quarrel and falling out with archpriest Isidore who was a friend of the Scetius monks. At the request of Bp. John of Jerusalem, Theophilus sent his friend Isidore to Palestine to mediate a dispute between Bp. John and Jerome. The mediation did not go well from which Theophilus developed an irritation toward Jerome. In the end Theophilus urged Jerome to respect the authority of Bp. John, a request he again made in 399.