Ninety-three patients, including 47 patients with Generalized Anxiety Disorder (GAD) and 46 patients with Major Depression (MD), were entered into recent clinical trials. Clinicians acknowledge that during the initial screening process, clear separation between depressed and anxious patients may be difficult. By using the DSM-IV criteria, the Hamilton Depression and Anxiety Scales, and a variety of other structured evaluations, patients were divided into the two diagnostic groups. The Millon Multiaxial Inventory (MCMI-III) was administered to all 93 patients as part of their initial assessment, but was not used in the diagnostic decision making process or in assignment to a particular clinical study. Upon completion of these studies, the Millon data were analyzed utilizing a cutoff score of 75, conforming to previous studies. Statistically significant differences in Millon personality patterns between MD and GAD patients included dependent, obsessive-compulsive, self-defeating, and borderline traits. Patients exhibiting dependent, self-defeating, and borderline patterns were statistically more likely to be included in clinical trials of MD rather than GAD. Also, patients with MD were more likely to disclose clinical information and exhibit self-critical behavior when compared to those with GAD. These results suggest that the MCMI-III may detect personality differences between anxious and depressed outpatients presenting for clinical trials.