The difficult doctor-patient relationship and "difficult patients" have been the subject of considerable anecdotal study. Reliable methods for identification of difficult patients have not been available for the empirical study of their prevalence and characteristics. We developed the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ), composed of 30 Likert items, completed by physicians after encounters with patients. Adult patients and their providers in an academic, municipal hospital clinic participated in the instrument development (n = 92), reliability (n = 224), and assessment of patient characteristics phases (n = 113) of the study. The DDPRQ was shown to be a reliable, practical instrument. Factor analysis revealed 5 dimensions with face validity. The DDPRQ classified 10.3-20.6% of patient encounters as "difficult" depending on the sample. Demographic characteristics, provider characteristics and most medical diagnoses were not associated with DDPRQ score. In contrast, difficult patients were characterized by psychosomatic symptoms, at least mild personality disorder, and Axis I (major) psychopathology, and most had more than one of these characteristics. The need to identify and understand these components of difficult patient behavior and to include the doctor-patient relationship in strategies for managing the difficult patient is discussed.