BACKGROUND/OBJECTIVE: "By-the-way" syndrome, a new problem raised by the patient at an encounter's closure, is common, but little is known about how physicians respond when it occurs. We analyzed the content of the syndrome, predictors of its appearance, and the physician response. DESIGN/PARTICIPANTS: Cross-sectional study of 92 videotaped encounters in an academic primary care clinic. RESULTS: The syndrome occurred in 39.1% of observed encounters. Its major content was bio-psychosocial (39%), psychosocial (36%), or biomedical (25%), whereas physician responses were mostly biomedical (44%). The physician response was concordant with the patient's question in 61% of encounters if the content of the question was psychosocial, 21% if bio-psychosocial, and 78% if biomedical; 32% of physicians solicited the patient's agenda two times or more in the group without, versus 11% in the group with, the syndrome (P = 0.02). In 22% of the encounters, physicians did not give any answer to the patient's question, particularly (38.5%) if it was of psychosocial content. CONCLUSIONS: "By-the-way" syndrome is mainly bio-psychosocial or psychosocial in content, whereas the physician response is usually biomedical. Asking about the patient's agenda twice or more during the office visit might decrease the appearance of this syndrome.