BACKGROUND:Patients commonly present to their physicians with medically unexplained symptoms (MUS), and there is no consensus about how physicians should interpret or treat such symptoms. OBJECTIVE: To examine how variations in physicians' interpretations of MUS are associated with physicians' religious characteristics and with physician specialty (primary care vs. psychiatry). DESIGN AND PARTICIPANTS: A national survey of a stratified random sample of 1,504 primary care physicians and 512 psychiatrists in 2009-2010. MAIN MEASURES: The extent to which physicians believe MUS reflect a root problem that is spiritual in nature or result from conditions that scientific research will eventually explain, and whether such patients would benefit from attention to their relationships, attention to their spiritual life, taking medications, and/or treatment by physicians. KEY RESULTS: Response rate was 63 % (1,208/ 1,909). More religious/spiritual physicians were more likely to believe that MUS reflect a spiritual problem (55 % for high vs. 24 % for low spirituality; OR=2.8, 1.7-4.5) and that these patients would benefit from paying attention to their spiritual life (79 % for high vs. 55 % for low spirituality; OR=3.1, 1.8-5.3). Psychiatrists were more likely to believe that scientific research will one day explain MUS (66 % vs. 52 %; OR= 1.9, 1.4-2.5) and that these symptoms will improve with treatment by a physician (54 % vs. 35 %; OR=2.4, 1.8-3.3). They were less likely to believe that MUS reflect a spiritual problem (23 % vs. 38 %; OR=0.5, 0.4-0.8). CONCLUSIONS: Physicians' interpretations of MUS vary widely, depending in part on physicians' religious characteristics and specialty. One in three physicians believes that patients with MUS have root problems that are spiritual in nature. Physicians who are more religious or spiritual are more likely to think of MUS as stemming from spiritual concerns. Psychiatrists are more optimistic that these patients will get better with treatment by physicians.