Much of the scientific literature on affective states in primary care settings is derived from instrument-based diagnoses, typically without the benefit of clinical in-depth examination. In a naturalistic family practice setting, we prospectively evaluated 108 consecutive anxious and/or depressed patients. All diagnoses derived from semistructured interviews conducted by a family physician with enhanced training in mood disorders. Nonbipolar depressions were found in 60 of 108 patients (55.6%), nearly half of whom were in the depression not otherwise specified (DNOS) category; yet on careful history, all but two of 28 DNOS cases had major depressive episodes in the past. Twenty-eight patients (25.9%) were diagnosed with bipolar I, II, or III disorder or cyclothymia. Panic disorder was found in 9%, and obsessive-compulsive disorder and active chemical dependency were each diagnosed in 3%. Bipolar spectrum disorders were common (one in three within the depressive group) and at times were not recognized until several weeks or months into the treatment phase of the depressed or anxious state. Although the largest percentage of patients had DNOS at the index episode, bipolar illness (usually bipolar II) was also common. Our findings contrast with the nearly total unipolarity reported in the instrument-based (nonclinician) literature. If generalizable, our observations have significant implications for physician education and practice, since bipolar depressions require different interventions. Further investigation to explore interview approaches and/or instruments sensitive for hypomania and other "soft" bipolar features seems warranted.