1. 1. As an alternative to the bipolar I/II distinction, a subtyping of bipolar affective disorders according to the sequence of polarity (mania or depression) has been proposed. In a study of 9J patients with bipolar affective and bipolar schizoaffective disorders we tested the stability of a subtyping using the sequence of polarity. Furthermore we investigated its relationship to bipolar I/II subtypes and to response to stabilizing therapy with lithium. 2. 2. In the individual patient the first sequence of polarity significantly predicted the same sequence of polarity of further manifestations. However, only half of the patients could be classified as either MDI (mania-depression-interval) or DMI (depression-mania-interval). Subtyping according to the sequence of polarity was not significantly related to the bipolar I/II subgroups. 3. 3. MDI patients showed a significantly better response to stabilizing therapy with lithium than DMI patients. 4. 4. Our findings lend support to the notion that the polarity sequence is of clinical relevance. The observed association between polarity sequence and effectiveness of lithium prophylaxis could be linked to direct consequences of a MDI or DMI sequence ( e.g.: different treatment approaches). On the other hand, a difference in polarity sequence might be the clinical expression of a difference in the underlying mechanisms of dysregulation, which in turn might be more or less prone to respond to lithium therapy.