• From 249 psychiatric patients with the diagnosis of manic-depressive disease a consecutive group of 100 were selected by systematic criteria. They were compared with a control group of 50 patients hospitalized with diagnoses of recognized medical diseases. Data were obtained by clinical examination, laboratory tests, and questionnaire. The mean age of onset for men was 41.2 years and for women 41.4 years, and no evidence was found to justify the continued use of the phrase "involutional melancholia" as implying that there is anything distinctive about the depressions of women near the menopause. The frequency of each individual symptom was studied. Many "medical" symptoms, such as headache and abdominal pain, were as frequent in the manic-depressive group as in the medically sick controls. The most significant differences related to poor concentration, poor sleep, and low mood, which were more frequent in the manic-depressive group. Fear of "losing mind" occurred as a feature of manic-depressive disease. Spells of various kinds were common in these patients, and the "anxiety attacks" that occurred in about one-third of them were extremely rare in patients with medical disease. The patient's own impression as to the precipitating event was usually clearly wrong or improbable. Increase in alcoholic ingestion was common in the manic-depressive patient. Family history showed significantly more "alcoholic" fathers. At least part of the problem called "alcoholism" seems related to manic-depressive disease. Some symptoms, such as thoughts of suicide and poor concentration are rare in medical patients and characteristic of the manic-depressive patient. The consequences of this illness include alcoholism, losing jobs, marital infidelity, unhappy marriages, business failures, lawsuits, and automobile accidents, among others. These serious consequences, the worst of which is death by suicide, make it important for doctors to learn to diagnose this common disease accurately. This can be done by the simple clinical pointers presented here. Knowledge of these facts is essential for the diagnosis and treatment of manic-depressive disease, one of the commonest of psychiatric disorders.