Two hundred and seventy-five male CBA/Birmingham mice including 84 mice over 80 wk of age were autopsied at intervals over the whole range of their natural life span of about 2 1/2 yr. Body weight increased progressively up to 30 wk of age when a plateau value of 30-40 g was attained. Subsequent to 80 wk a slight, progressive decrease was observed. The thymus showed a profound increase in size from about 5 mg at birth to approximately 60 mg by the 3rd wk. Thereafter, the weight of the thymus decreased, rapidly at first, to reach 20-30 mg by 15 wk of age. The thymus weight then decreased more slowly to around 10 mg by the 80th wk. The spleen weight reached a plateau value of 50-60 mg by 4 wk and this was maintained until the 80th wk. In mice older than 80 wk varying degrees of splenomegaly were observed. Histologically, the areas of white pulp in these spleens were very prominent, suggestive of an on-going immune response. It was possible to associate this splenomegaly with the appearance of gross and microscopic evidence of hepatomas. No hepatomas were observed prior to 80 wk, but between 80 and 120 wk the incidence increased progressively; and all the mice whose age at autopsy exceeded 120 wk had hepatomas. Histologically the hepatomas showed marked nuclear plemorphism with occasional mitotic figures. Thrombi, areas of avascular necrosis and collections of inflammatory cells were observed. The tumour metastasised to the lung in 12% of cases. The doubling time of the hepatoma in situ was estimated as 1-6 wk (range 1-3-1-8 wk). These hepatomas were transplantable and grew with a doubling of 2-25 wk in syngeneic adult recipients. To test if the more rapid progressive growth of the tumour in situ in old CBA mice might have resulted from a breakdown in "immunological surveillance" the same tumour was transplanted simultaneously to a group of young and old recipients. The tumour grew more slowly (doubling time, 2-5 wk) in the old recipients. This result would not appear to support the hypothesis of a prolonged breakdown of immunological surveillance as the cause of the progressive increase in the incidence and growth of these tumours in situ in old mice.

The effects of irradiation on the haematopoietic tissues of anaesthetized mice have bee measured using the balance between damage and recovery during the 10-day period following the administration of various doses of whole-body- X-irradiation. The cellularity of the femoral bone marrow, the weight of the spleen and the number of (endogenous) spleen colonies are elevated in animals anaesthetized using Avertin during exposure to doses of whole-body X-irradiation in the range between 400 and 850 rad, with a dose reduction factor of 1.2–1.4

Groups of mice have been autopsied at regular intervals during the period of lymphomyeloid tissue regeneration which follows the phase of hypocellularity induced by the i.v. injection of 100 μg (4 mg/kg bodyweight) nitrogen mustard. The marrow cellularity recovered to levels in the normal range by the 8th day and remained in this range up to the 40th day. Subsequently, the marrow showed a slight degree of hypocellularity up to day 120. Granulocytes were predominant during the initial phase of marrow regeneration from days 5–12. The thymus, lymph nodes, and spleen commenced regeneration during the second week post‐injection. The thymus exhibited periodic size variations such that it was substantially larger than the thymus of age‐matched controls from 20–30 d, 46–73 d, and 75–100 d after injection. The lymph nodes and lymphoid tissue of the spleen regenerated only slowly to reach control values by 40–50 d. Superimposed on the recovering lymphoid tissue of the spleen was a phase of erythroid hyperplasia lasting from 10–18 d post‐injection. This coincided with a shift from granulocytosis to erythroid hyperplasia in the marrow. This erythroid hyperplasia lasted until day 30 when the cellular composition of the marrow and spleen returned to normal. A possible explanation of these results is that nitrogen mustard introduces a degree of synchrony into stem cell proliferation and differentiation. Additionally, these results emphasize the role of the haematopoietic microenvironment in the control of stem cell differentiation.