Summary1. There is convincing evidence that a number of agents such as bacteria, viruses, endotoxins, foreign proteins, smokes and chemicals come into contact under physiological conditions with the lymphoid tissue associated with the gut and/or bronchial systems. Endogenous lectins and proteases may also act as mitogens on the central and peripheral immune system.2. It is suggested that these agents act as inducers of interferon (and some also as immunogens), so that local production of interferon is turned on successively from cell to cell depending upon their responsiveness and upon the periodic inflow of inducers.3. On the basis of a number of different features, it is proposed to distinguish between an ‘acute’ and a ‘physiological’ interferon response. In the latter, the interferon‐producing cell influences the neighbouring cells by short‐range humoral transmission (paracrine control) and possibly by cellular interaction, while the route of the general circulation is preferentially used in the former response.4. It is suggested that the physiological interferon response, although previously overlooked, has great biological importance because production of interferon at strategic sites can maintain active defence systems essential for survival.5. It is to be expected that the physiological interferon response, although amenable to experimental verification, may be difficult to detect. On the basis that interferon is normally absent from serum, it is suggested that most of the released immune‐type interferon is either bound by cells surrounding the site of its synthesis or catabolized locally.6. It is postulated that the progressive decline of the physiological interferon response with increasing age may represent one of the factors favouring the insurgence of autoimmune diseases and tumours in the process of ageing. It is also suggested that the involution of the thymus may in part be due to intrathymic production of interferon induced by proteases released fro