Irenaeus, head of the Christian community at Lyon in Gaul, was a central figure in the second-century debate stimulated in the Christian churches by gnosticism and by the teachings of Marcion. One may assume that Irenaeus' hostility to Christian gnosticism as well as to the teachings of Marcion was brought with him from Asia. In his Ecclesiastical History, Eusebius of Caesarea mentions a number of writings of Irenaeus. Irenaeus 'New Testament' is basically a collection of works conceived to be written by, or to report the teaching of, apostles; and while he differs radically from Valentinians about how such books should be read, he does not, save in the case of the Acts, seem to differ with them about the books that constitute the core list. It is Marcion, not the gnostics, whom he openly accuses of truncating the list of essential Christian Scriptures.

Christian contact with the Sethian Gnostics must have occurred rather early, for by 125 CE one finds Basilides of Alexandria expounding a sophisticated and completely Christian Gnostic theological system. His younger contemporary, Valentinus, likewise developed a wholly Christian Gnostic theology, which reached a high level of sophistication in the work of his pupil Ptolemaeus. One of the first things to strike a reader of Gnostic literature is the vast number of metaphysical entities. One such is the Apocryphon of John that is an early example of what may be called classic Sethian Gnosticism. The Christian philosopher and earliest commentator on early Christian writings Basilides of Alexandria was, in the words of Hegel, 'one of the most distinguished Gnostics'. Ptolemy was described by St Irenaeus as 'the blossom of Valentinus' school'. The last mention of late-antique Gnosticism is to be found in a seventh-century Christian canon prohibiting certain sects, of which that of the Valentinians is mentioned by name.