Objective. To examine the prevalence, predictors, and consequences of physician detection of unannounced standardized patients (SPs) in a study of the impact of direct-to-consumer advertising on treatment for depression. Data Sources. Eighteen trained SPs were randomly assigned to conduct 298 unannounced audio-recorded visits with 152 primary care physicians in three U.S. cities between May 2003 and May 2004. Study Design. Randomized controlled trial using SPs. SPs portrayed six roles, created by crossing two clinical conditions (major depression or adjustment disorder) with three medication request scripts (brand-specific request, general request for an antidepressant, or no request). Data Collection. Within 2 weeks following the visit, physicians completed a form asking whether they "suspected" conducting an office visit with an SP during the past 2 weeks; 296 (99 percent) detection forms were returned. Physicians provided contextual data, a Clinician Background Questionnaire. SPs filled in a Standardized Patient Reporting Form for each visit and returned all written prescriptions and medication samples to the laboratory. Principal Findings. Depending on the definition, detection rates ranged from 5 percent (unambiguous detection) to 23.6 percent (any degree of suspicion) of SP visits. In 12.8 percent of encounters, physicians accurately detected the SP before or during the visit but they only rarely believed their suspicions affected their clinical behavior. In random effects logistic regression analyses controlling for role, actor, physician, and practice factors, suspected visits occurred less frequently in HMO settings than in solo practice settings (p<.05). Physicians more frequently referred SPs to mental health professionals when visits aroused high suspicion (p<.05). Conclusions. Trained actors portrayed patient roles conveying mood disorders at low levels of detection. There was some evidence for differential treatment of detected standardized patients by physicians with regard to referrals but not antidepressant prescribing or follow-up recommendations. Systematic assessment of detection is recommended when SPs are used in studies of clinical process and quality of care.