If virtually until the turn of the 20th century, the aetiology of communicable diseases was still hotly disputed even among outstanding medical scientists, evidently in earlier ages the intellectual and practical challenges that mass infections and epidemics posed to individuals and entire societies were far greater. In classical and medieval Islamic sources, it would appear that the rough empiricism of lay people often met such challenges more effectively than the frequently contorted and ideologically encumbered reasoning by scholars. With the appropriation of Galenic medicine, which supported naturalist notions of transmissibility, the earlier lay empiricism acquired a theoretical foundation—however shaky it must appear from a modern viewpoint—and became integrated into ‘academic’ discourse. There, it continued to be argued in opposition to increasingly narrow, tradition-bound and occasionalist interpretations of what was taken to be the Prophet’s and Companions’ precedent in dealing with the plague. In this paper, Ibn al-Khat?b of Granada (killed 1374 CE) and such contemporaries of his as Ibn Khald?n will be prime witnesses against the anti-naturalist trends ever more prominent in authors of the late Mamluk period (rebutting Justin Stearns, 2007). Further, the post-1500 developments of such trends will be discussed in view of the sudden appearance in the Middle East of syphilis as a novel communicable disease; attention will focus on opinions affirming the transmissibility of syphilis, such as those of Safavid medical authors. In conclusion, the paper will address the question of the relative impact of the variant viewpoints on social attitudes towards communicable disease—before the introduction of modern medicine into the Middle East.