BACKGROUND: Some primary care physicians provide less than optimal care for depression (Kessler et al., Journal of the American Medical Association 291, 2581-90, 2004). However, the literature is not unanimous on the best method to use in order to investigate this variation in care. To capture variations in physician behaviour and decision making in primary care settings, 32 interactive CD-ROM vignettes were constructed and tested. AIM AND METHOD: The primary aim of this methods-focused paper was to review the extent to which our study method - an interactive CD-ROM patient vignette methodology - was effective in capturing variation in physician behaviour. Specifically, we examined the following questions: (a) Did the interactive CD-ROM technology work? (b) Did we create believable virtual patients? (c) Did the research protocol enable interviews (data collection) to be completed as planned? (d) To what extent was the targeted study sample size achieved? and (e) Did the study interview protocol generate valid and reliable quantitative data and rich, credible qualitative data? FINDINGS: Among a sample of 404 randomly selected primary care physicians, our voice-activated interactive methodology appeared to be effective. Specifically, our methodology - combining interactive virtual patient vignette technology, experimental design, and expansive open-ended interview protocol - generated valid explanations for variations in primary care physician practice patterns related to depression care.