In 1587, Walter Raleigh, acting on behalf of the British monarch Queen Elizabeth I, made attempts at re-establishing a permanent colony at Roanoake island (now in modern-day North Carolina and part of the Outer Banks Islands) There had been a previous attempt in 1585 which failed due to food shortages and lack of other supplies etc.
From the beginning, the colonisation efforts were very problematic. As might be expected, there were already indigenous Amerindian people living in the area, and the British not only antagonised them (and in at least one case committed an execution), they also inadvertently introduced Western diseases to local villages, with devastating results.
When a re-supply vessel arrived from England three years later, the crew found that every one of the 100 or so residents had disappeared.
There are various theories about their disappearance, suggestions include :
None of the theories currently has general scholarly support - the disappearance is considered unexplained.
Wikenigma has not been able to source many peer-reviewed research papers on the subject. Here is one (paywalled) example from The North Carolina Historical Review,Vol. 78, No. 1, pp. 67-83.
There are, however, numerous other publications on the subject. See, for example Exploring the Migration of the Roanoke Colonists (archived)