We employ a structural equation model to examine the relationship between academic performance and depressed mood over 4 years for a single medical school class. Academic performance measures included undergraduate gradepoint average, first- and second-year medical school gradepoint average, full Medical College Admissions Test (MCAT) and total National Boards Part I (NB) scores. Severity of depressed mood was assessed by administering the Beck Depression Inventory two times per year during the first 2 years, and once per year during the last 2 years. Overall there is little reason to think that depressive mood states compromise academic performance during the first 2 years of medical school for the class as a whole. Medical school grades had no direct impact on depressed mood, and mood had no direct impact on grades. There was a non-significant tendency for mood in the months preceding National Boards Part I to influence Board scores, which in turn influenced mood. Students with higher college gradepoint averages consistently reported fewer depressive symptoms throughout medical school. The latter result directs attention to a subgroup of medical students less susceptible to depression, or less prone to admit distress or symptoms. The non-susceptible and/or minimizing qualities of this subgroup merit further investigation.