Brisket disease, an affliction of cattle, is important because of : (1) economic losses, (2) similarities to chronic mountain sickness in humans, and (3) the provision of experimental animals for cardiac research. In afflicted cattle, right cardiac ventricular hypertrophy and dilatation occur and are manifestations of attempted compensation for reduced alveolar oxygen by increasing pulmonary circulation. Geographic variations in occurrence of brisket disease in Utah indicate that hypoxia is not the sole causative factor. From the findings that afflicted cattle exhibit hypocalcemia and hyperkalemia, and the disease occurs most commonly in wet meadowland environments where potassium is high and calcium low in browse, a dual stress theory of cause was hypothesized; i.e., altitude-induced hypoxia plus ionic calcium-potassium imbalance. To test the hypothesis, 40 Hereford calves were randomized into four equal groups, two at 1,372 meters (normal) and two at 2,745 meters (hypoxic) elevation. At each elevation there were control (balanced) and treated (calcium-potassium) groups. For 16 weeks, treated calves received, by diet, one-fourth the calcium and 10 times the potassium requirements; also, repeated injections of dipotassium ethylenediaminetetraacetate, potassium chloride, and an aldosterone inhibitor to further induce hypocalcemia and hyperkalemia. Control groups at each elevation received a balanced diet and no injections. Since optimal myocardial function is dependent upon proper ion balance, and concentrations of calcium, potassium, sodium, phosphorus, magnesium, chloride, iron, zinc, and copper in blood, heart, liver, kidney, and bone are indices, these elements were quantitated. Calcium concentration in serum was reduced by 1.6 milligrams per 100 milliliters from an initial value of 9.4 milligrams per 100 milliliters, and an average increase of 1.8 milliequivalents per liter in potassium concentration in whole blood, from the initial concentration of 12. 4 milliequivalents per liter, occurred in treated calves . Elevation caused an increase of 1.7 milliequivalents per liter in potassium concentration in serum from the initial concentration of 6.2 milliequivalents per liter. Iron concentration in whole blood increased in response to hypoxia and decreased due to treatment. In the serum, sodium and copper decreased and chloride increased due to treatment. Compared to low elevation, significant tissue compositional changes in calves at high elevation were as follows: (l) calcium: kidney 12 percent higher, heart 9 percent lower: (2) sodium: liver 5 percent lower, kidney 3 percent higher: (2) phosphorus: kidney 2 percent higher. More profound changes occurred in cattle subjected to treatment: compared to controls, the tissue compositions in imbalanced cattle were as follows: (1) calcium: heart 10 percent and liver 13 percent lower, kidney 92 percent higher; (2) potassium: heart 13 percent higher, liver and kidney 6 percent lower; (3) sodium: heart 18 percent, liver 8 percent, and kidney 14 percent lower; (4) magnesium: heart 20 percent and liver 5 percent higher, kidney 11 percent lower; (5) phosphorus: heart 6 percent and kidney 21 percent higher, liver xvi 2 percent lower; (6) absolute dry matter: liver 5 percent and kidney 13 percent lower; (7) total ash: kidney 4 percent lower. In addition, iron, zinc, and copper were decreased in both cardiac and hepatic tissues of treated calves. Treatment influenced bone ash composition as follows: compared to controls, calcium decreased to 25.3 from 32.5 percent; phosphorus decreased to 16.5 from 19.0 percent; potassium increased to 0.16 from 0.08 percent; and zinc increased to 319 parts per million from 227 parts per million. High altitude was also influential. Compared to controls, phosphorus increased to 18.1 percent from 17.5 percent, potassium decreased to 0.112 from 0.129 percent, sodium to 1.09 from 1.17 percent, and magnesium to 0. 64 from 0.70 percent.