The myocardial ultrastructural alterations produced by monensin toxicosis in cattle were characterized. The initial ultrastructural alterations developed from 1 to 11 days after dosing and consisted of extensive sarcoplasmic vacuolization from mitochondrial swelling and lipid accumulation. By day 4, many damaged myocytes also contained dense, compact myelin figures. From day 4 to day 11, myocardial necrosis developed gradually, and the necrotic myocytes appeared either as dense fibers with intact sarcomeres or disrupted fibers with hypercontraction bands. Macrophages invaded the areas of necrosis and lysed fragments of necrotic myocytes. Monensin toxicosis provides a useful model for studies of drug-related myocardial injury.