There are several literal references to illness in this story. Besides Daisy's malaria, Mrs. Miller and the rest of the family (excluding Daisy) suffer from dyspepsia, a common gastric ailment in prosperous nineteenth-century Americans, although the mother's dispirited, low-energy affect, difficulty sleeping, and nerves suggests what we would now see as depression.

But what makes this story interesting is the way James uses illness to figure sexual contamination and social disfavor. Although Daisy eventually succumbs to what was termed "Roman fever," her malaria merely literalizes her supposed infection with a different kind of "fever," which the American expatriates and tourists have already diagnosed--a fever brought on by her apparently "light" (loose) sexual escapades with Italian men. James's story, posed as a case "study," illuminates how our culture imagines sexuality as a kind of disease that, past a certain point, is deemed fatal.

As Winterbourne, and the reader, cast about for an adequate "diagnosis" for Daisy, his difficulty implicitly interrogates the cultural categories we feel compelled to apply to women in particular. He considers, and discards, the terms "an American girl," "coquette," "innocent," "flirt," "common," "ignorant," "bad," "vulgar," "a nice girl," and "a young lady du meilleur monde" to describe Daisy, before settling on "a young lady whom a gentleman need no longer be at pains to respect" and "a clever reprobate." Sadly, by the time Winterbourne realizes that his diagnosis was wrong, the patient is dead.