The effects of the long term alloxan administration and hypophysectomy on the pancreatic islets of the male rat (Donryu strain) were studied biochemically and cytologically. For the fixation LEVI's, BOUIN's fluid and ZENKER-formol were used and 3-4μ thick paraffin sections were stained with azan aldehyede-fuchsin-light green-orange G (AFLO) and chromealum-hematoxylin-phloxin (CHP) and by the periodic acid-SCHIFF reaction (PAS) for the demonstration of glycogen in the islet cells. The argyrophil A₁ cells were demonstrated by the silver-impregnation method after HELLMAN et al. (1960). The results were as follows:<br>1. The islets of normal rats (5 control rats) were oval or spherical in shape and showed various sizes. Many capillaries surrounded by a small amount of connective tissue entered the innermost part of each islet. In the normal rats the islet cells chiefly consisted of B cells; a large number of B cells occupied the major internal part of the islet, while a small number of A cells were localized only at the peripheral parts of them making one to three incomplete thin layers.<br>2. To three male rats 150mg/kg alloxan was given subcutanously every other day for one month (15 times). Blood sugar level measured with anthrone reagent at 24 hours after the last injection was about four times high as that of control group. Histologically there was found remarkable increase in A cells, distributed not only in the periphery of the islet but also along the walls of the capillaries even in the center of the islet. On the contrary B cells decreased in number, though there were many large, sometimes extraordinary large B cells among remaining ones. In all B cells intense decrease in β granules was demonstrated (high degranuration of B cells). In some swollen and enlarged B cells the vacuolization of cytoplasm was encountered, and in severe cases they appeared as if they had fallen into so called ‘hydropic degeneration’. It was proved that the vacuolization (hydropic degeneration) of B cells was derived from the glycogen infiltration of B calls.<br>In one case sacrificed at 72 hours after 14 times alloxan injections the blood sugar level was about the same as in the control animals, but A cells were slightly increased, having a tendency to enter along the capillaries into the internal parts of islets. B cells were slightly decreased and their enlargement and vacuolization were scarcely found. Decrease in β granules was also slighter than in the 15 times alloxan injected group.<br>3. In the second experiment one month old male rats were hypophysectomized and sacrificed five months later. Their body weights became about one third, and blood sugar level about one half those of the control rats. Histologically atrophy of islets was not recognized. Size, number and distribution of A and B cells were revealed almost as normal. Any marked morphological changes of islets, especially of A cells due to hypophysectomy, were not observed. The considerable decrease in β granules was observed, but not so remarkably as in alloxan groups.<br>In one of hypophysectomized rats, necropsy disclosed that only adenohypophysis was removed. In this case decrease in body weight was slight, and the almost normal blood sugar level was maintained, but histological changes were similar to those in the perfectly hypophysectomized group.<br>4. HELLMAN's argyrophil A₁ cells both in control and hypophysectomized group appeared in a small number scatteringly between the peripheral A-cell layer and the central B-cell group. The numerical rate of A₁ cells to the total islet cells was 4.4% in control group. It showed about 2 times increase and reached 9.6% in hypophysectomized group (8.7% in adenohypophysectomized one). In alloxan group A₁ cells were found in the largest number among the remarkably proliferated A cells which had invaded along the capillaries into the central parts of islet.