Interferon-alpha (IFN-alpha) treatment in both oncological and hepatological settings is associated with depression. If IFN-a treatment induces depression in high numbers, it could serve as a model for studying the pathophysiology of depression, in general. The authors therefore studied 43 oncology patients treated with standard or pegylated IFN-a with baseline psychiatric assessment and at regular time-points in the first 6 months of treatment. Apart from a severe depression because of brain metastases, authors observed only two clinically relevant depressive states. Contrary to findings in most of the literature, most depressive episodes in this study were self-limiting and short-lasting and were associated with either episodes of flu-like symptoms common at the start of the treatment or with concurrent psychosocial events. In the group as a whole, scores on both observer-based and self-report rating scales did not show clinically relevant changes. The results of this study indicate that IFN-a treatment is not suitable as a study model for depression in general.