We studied 569 patients with RDC non-bipolar major depressive disorder from the clinical portion of the NIMH Program on the Psychobiology of Depression. Primary (n = 327; never had a non-affective disorder), secondary (n = 191; had a non-affective disorder before ever having a major depressive episode), and "complicated' (n = 51; had at least one depressive episode before and another since developing a non-affective condition) patients were compared on demographic variables, past episodes of depression, past treatments received, and symptoms seen in the index episode. For most characteristics, the groups fell in the order primary, secondary, complicated, such that complicated cases had the earliest onset, the longest duration and the greatest severity in the index episode. These data do not discriminate between two hypotheses: that secondary and complicated depressions are basically depressions which happen to occur in a non-affectively ill person, or that they are different disorders which are distinguished clinically by characteristics related to severity.