In its examination of a selection of 18th-century medical treatises and women’s writing, this essay considers a range of context-specific and historically specific medical vocabularies and tries to illuminate the various linguistic registers of physicians’ and women’s understandings and experiences of physio-emotional illness. In a preprofessionalised world in which medical and literary cultures overlapped significantly and medical knowledge was not yet restricted to a group of formally trained male elites, vocabularies of illness abounded, oftentimes moving freely between the permeable disciplinary boundaries of the age. Physician writers, in their efforts to define and label the cluster of related conditions commonly known as spleen, vapours, melancholy, or hypochondriacal and hysterical affliction, often operated on a principle of humility, embracing uncertainty, admitting fault and assuming a willingness to question their own assumptions. They recognised that elusive processes were at the heart of these conditions, which came with a vast amalgam of physical and psychological symptoms, as well as a long list of possible designations. For their part, Anne Finch, Lady Mary Wortley Montagu, Hester Lynch Piozzi, Elizabeth Carter, Mary Leapor, Elizabeth Tollet, Anna Seward and Susanna Blamire interpreted with a keen eye the medical information available to them, deployed the plethora of words at their disposal and created their own vocabularies of illness. As they formulated a productively unstable, fluctuating lexicon to conceptualise and define spleen and its analogous conditions, these women writers came up with new words and inventive metonyms, and drew at once on the language of medicine, social and domestic inequality, and the natural world to capture experiences of suffering.