He had, in the meantime, been promoting pre-evangelization work among the natives – winning their goodwill by various forms of kindness, erecting crosses which well-rehearsed soldiers were commissioned to explain to the Indians, deputing some of his better-prepared men to attempt to introduce the Indians to the chief tenets of Christianity. Though at times there were noted some heartening evidences that the natives were indeed responding to such overtures, in general the nomadic life of these children of the forest was a persistent difficulty.

The first group of Jesuit missionaries to arrive in La Florida left Spain in July of 1566: it was composed of two priests and a lay brother. Tragedy attended their very arrival. When the vessel they were traveling on failed to find the harbor of San Agustin, the Superior of the group, Father Pedro Martínez, with some seamen set out in a small boat to seek directions. A sudden violent storm drove the vessel on which they had arrived out to sea, leaving them stranded on the shore. Some two weeks later, begging some fish on San Pedro (Cumberland) Island, the priest and several of the sailors, were murdered by the natives. The first Jesuit mission was inaugurated with the death of its superior.

News of the slaying of Father Martínez, when it reached Spain, caused a surge of. apostolic missionary zeal among the Jesuits: many volunteered to take the place of the slain missionary. In 1568 the General of the Jesuits named eleven religious – three priests, three lay brothers, five novices – to join the two already in La Florida. The superior of this second group, Father Bautista de Segura, had a clear plan for developing the Florida mission, but in the face of the indifference of the natives the well-laid plan failed to give results. Father Rogel, the surviving priest from the first group, carried the apostolate to Orista, the territory to the north of Santa Elena, which at first seemed a promising field. Added to the inherited vices of these pagans was an unexpected social problem: by nature the natives were migrants, who enjoyed moving from place to place according to the different seasons. Under these conditions the Jesuits came to despair of establishing an effective Catholic community.

Disheartened with the situation, two years after the arrival of the second group of Jesuits, Father Segura led seven of his companions farther north, seeking a more receptive group of natives. They established themselves at the Indian village called Axacan (thought to be near present-day Fredericksburg, Virginia). Within six months, before they had had the opportunity of winning any souls for Christ, in February of 1571, Father Segura and his seven companions all were slain by the natives. St. Francisco de Borja in 1572 closed out the abortive Jesuit mission by withdrawing the two remaining members of the society.⁸