This thesis examines interactions between science and the supernatural in Huysmans’s Durtal tetralogy. The protagonist, whose aesthetic and philosophical starting point is naturalism, converts to Catholicism. This unusual conversion reflects social upheavals contemporary with Huysmans’s cycle of novels. In the late nineteenth century, science, emerging as symbol of new hope and salvation for humanity, has in a sense replaced religion. The Durtal cycle catalogues the disorders generated by this replacement, and represents the creation of a new order more suited to Durtal’s persona, through deconstruction of existing codes and beliefs. Thus is shaped the intellectual and aesthetic matrix of the four novels. Pathology is at the intersection of the interactions between science and the supernatural, the various components of which constitute the subject of the three substantive chapters of the thesis. Figuring social degeneration and the creation of imaginary medical worlds founded on contamination, Huysmans’s text explores the boundaries between science and religion, thus offering a new cosmogony constructed around a concept of mystic substitution associated with Catholicism. Analysis of these textual explorations is followed by a study of the body and the soul as the two primary principles contributing to the conflicts articulated in Huysmans’s work. The conversion processes to which the body and the soul are subjected help to build renewed relationships between the material and the spiritual, the visible and the invisible. Writing thus appears as the result of an alchemical quest in which opposites can ultimately be reunited. The thesis concludes with a discussion of the development of the novel form, subject to so many contradictory influences. The pharmaceutical quality – in Derridean terms – of writing ends this crisis and restores the author’s authority, making of the Durtal tetralogy a work that is characterised at one and the same time by its naturalism and by its mysticism.