Mechanical alternans developed spontaneously in 5 of 17 right ventricular papillary muscles from atherosclerotic rabbits. The rabbits had eaten an atherogenic diet of 5% lard, 5% peanut oil, 0.5% cholesterol, and 89.5% rabbit pellets for 116-184 days. In one muscle mechanical alternans developed slowly and persisted. When the condition had developed fully, in the weaker contraction the muscle shortened only 20% as far when contracting isotonically and developed only 38% as much tension when contracting isometrically. Added to the superfusate, calcium (5.0 mM) or norepinephrine (1.5 X 10(-5) M) abolished the alternans. In four muscles mechanical alternans was only temporary. Compared with the 12 muscles that did not develop alternans, these 4, when contracting isometrically 12 times/min but not in alternans, had longer latency and required more time to develop tension at the maximum rate and to develop peak tension. Contracting isotonically, they required more time to accelerate to maximum velocity of shortening and to shorten maximally. Raising the contraction frequency to 24/min decreased the differences in performance between the two groups. Norepinephrine (1.5 X 10(-5) M) made the differences smaller still. We think that both the mechanical alternans and the differences in performance between the muscles that developed alteranans and those that did not resulted from a defect in the cardiac cell's handling of calcium. Diet-induced changes in the lipid composition of the sarcoplasmic reticulum or sarcolemma or both seem probable causes.