Abstract: William H. McNeill, a prestigious expert on world history has raised a theory that the establishment of the caste system might be associated with plagues. Based on this theory, we further hypothesize that the concept of "cleanliness" in Hinduism might originate from a lower risk of infection. To decrease their own risk of infection, the politically and economically dominating higher castes established the cross-caste segregation and systematic discrimination against groups of higher risk. Such segregation and discrimination, under the influence of other socioeconomic factors, eventually evolved into the persistent caste system. In the end, the legal texts in Manusmriti demonstrate that this hypothesis would be at least reasonable to explain the origin of the critical concepts of "cleanliness-filthiness" in the world view of Hindu.