Describes an empirical approach to the study of monothematic delirium and its premises of basic etiology, rationality, and conservation of significance. The empirical approach considers that the proximal cause of a delirium belief is an extreme isolating experience. Delirium beliefs are a rational response to this isolating experience, and the terms used by delirious people to express a delirium belief conserve their normal significance. Clinical data that support the empirical approach to delirium are discussed in addition to criticisms of the empirical approach and reactions to the criticisms.