Primary care physicians have many questions about optimal care while they are seeing patients, but they pursue only about 30% of their questions. The authors designed a study to determine the factors that motivate physicians to pursue answers to some of their questions, while leaving the majority of their questions unanswered. They interviewed 49 non-academic primary care physicians during office hours to record clinical questions as they arose in the course of patient care. The physicians then recorded their perceptions of each question with respect to 12 factors expected to motivate information seeking. Two to five days after the interview, each physician was telephoned to determine which questions had been pursued. In a multiple logistic-regression model only two factors were significant predictors of pursuit of new information: the physician's belief that a definitive answer existed, and the urgency of the patient's problem. Other factors, including the difficulty of finding the answer, potential malpractice liability, potential help or harm to the patient, and self-perceived knowledge of the problem, were not significant in the model. Primary care physicians are significantly more likely to pursue answers to their clinical questions when they believe that definitive answers to those questions exist, and when they perceive the patient's problem to be urgent. Medical information systems must be shown to have direct and immediate benefits to solving the problems of patient care if they are to be more widely used by practitioners.