Despite dramatic clinical improvement in about one-third of a group of severely depressed, medication-resistant patients one year after modified leucotomy, their relative decrease in conjugated and free tyramine output after an oral tyramine load remained unchanged and abnormal. Whilst a direct deficit in intestinal tyramine-conjugating ability still needs to be finally ruled out, this appears most compatible with a deficit due to bodily metabolic failure, perhaps a deficit in membrane transport which could be an essential aspect of the depressive illness syndrome. Attention is drawn to a similar defect in migraine. The two illnesses may represent a common predisposition which an appropriate triggering mechanism may transform to the florid disease. Biochemical detection of such vulnerability may have important diagnostic and predictive significance.