5. Irradiation would advance such an increase of the histohematic barrier and ensuing consequences, to various degrees in various tissues, depending on the sensitivity of the constituent parenchymal cells. Non-specific damage to the endothelium of the fine vasculature directly or indirectly caused by radiation would be the primary cause. The consequent morphological (intersti- tial edema, increased fibrillar density, spotty at first and then more generalized) and functional changes (loss of reserve capacity of single organs reflecting gradually and progressively on other parts or on dependent organs ) would tend to perpetuate and to increase themselves by circular reactions where the natural and radiation-induced aging would not be separable any longer. 46. The basic notions of Casarett's model [C7] appear on the whole biologi- eally well founded, since it is known that radiation may cause an interstitial fibrillar density and capillary fibrosis. The mechanisms of these phenomena have recently been discussed by Gerber [G1] who has examined the possible pathways responsible for fibrosis and by Hopewell addressed himself to vascular changes. |H16] who has particularly But whether the initial endothelial and connective changes operating in natural and in radiation-induced aging may indeed be the same remains to be demonstrated and so do the further steps of Casarett's hypothesis, which should be set on firmer ground /W1]. In addi- tion, more recent information on the radiosensitivity of the endothelial cells [R11] seem to cast considerable doubt on the applicability of the hypothesis to the very low doses and dose-rates and to confine presumably its interest to the region of the intermediate to high doses. 7. The hypothesis could also be entertained that late effects of radiation on the duration of life might be brought about viaalterations of the immune system and in this respect two possible mechanisms of action could be envisaged. The first would imply auto-immune diseases as possible causes of a diffuse deleterious action; alternatively, life-shortening could be viewed as the result of an earlier appearance and a higher incidence of tumours, elicited in turn by radiation-induced immune disturbances. In no case would the effect of life-shortening have a truly non-specific character, because an acceleration or an advancement in time of old-age diseases without changes in their spectrum could hardly be expected as a result of such mechanisms. 48. In 1972 the Committee reviewed extensively the effects of radiation on the immune response and considered the general question of radiation as it