One hundred female rats were obtained from the Sprague-Dawley Company when they were twelve to fifteen months old. These were discarded breeders which had each cast six or more litters. We were primarily interested in the incidence of mammary tumors, and each rat was maintained until a tumor developed. Some of the rats had tumors at the time of arrival in the laboratory; others appeared at varying intervals up to a year, by which time all rats had developed tumors and had been killed for autopsy. Temperature was maintained at 74°-78° F. The rats were fed Rockland rat diet pellets.

Tumors

One hundred per cent of the rats developed tumors of the mammary glands. One rat had a mammary carcinoma; the rest of the rats each had one or more fibroadenomas, benign tumors in that they do not metastasize, although they grow rapidly and are transplantable under certain conditions. One rat had a chromophobe adenoma of the pituitary, two rats each had an ovarian tumor, two rats each had a polyp of the uterus, and one rat had an uncharacterized tumor of the ophthalmic division of the trigeminal nerve.

Vascular

The blood pressure was measured under ether anesthesia just prior to autopsy by cannulating the carotid artery with polyethylene tubing, which was connected directly to a mercury manometer (U-tube) with a pressure-botde system. Fifteen of the rats were found to have mean pressures of 140 mm. of mercury or higher, the highest pressure recorded being 160. Gross changes in the aortae representing calcifying atherosclerosis were seen in ninety-seven rats. The vessels were whitish, dilated, and rigid. In many cases the gross changes extended throughout the arterial tree. Kinking in the mesenteric vessels was seen in ninety of the rats. The more extreme changes in the mesenteric and pancreatic vessels included clusters of thrombi resembling periarteritis nodosa. Whitish areas in the walls of the heart representing fibrosis were seen in four rats.

Kidneys

Pitting in the kidney caused in part by the dilation of tubules at the surface was seen in forty-six rats. In more affected cases the kidneys were mottled and nodular. The microscopic changes have been described. Eleven rats had renal calculi and two rats had unilateral hydronephrosis.

Stomach

Ulcers of the cardiac portion of the stomach were observed in twenty-five rats.

Adrenals- In ninety rats the surface of the adrenal glands was spotted and granular. Some of the microscopic changes in the adrenal cortices have been determined.

Eyes

Opacity of the lens was seen bilaterally in one rat and unilaterally in two rats. Marked exophthalmos with hemorrhage into the eyeball was observed in one rat and was found to have resulted from the tumor of the fifth nerve noted above.

The pathology described above occurred "spontaneously" in rats without infectious diseases. The temperature was optimal and diet was thought to be optimal. The frequent breeding of these rats may have been stressful, but otherwise these animals had been maintained without stress.

Attempts were now made to affect the incidence and severity of pathology by stressors and by stimulating the adrenal cortices with ACTH. Treatment of these rats with doses of repository forms of corticotropin (Depo-ACTH and ACTHAR Gel) or repeated exposure of rats to severe neuromuscular stress for periods of eight weeks failed to produce a significant change in the incidence and severity of pathologic change over that observed in control groups. It is felt that chronic obstructive nephropathy and ensuing electrolyte disturbances are probably important factors in the cardiovascular pathology observed in these aging, female breeder rats.