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In this study, we present evidence that cows fed highly cationic diets are less responsive to parathyroid hormone than those fed a highly anionic diet. Fortyseven Jersey cows (55 mo of age) were fed an alfalfa haylage-based diet supplemented with either anions (Cl^-) or cations Na⁺). Cows fed the high cationic diet suffered significantly more cases of milk fever (6 out of 23) than those fed the high anionic diet (1 out of 24). Concentrations of Ca at parturition and the first 2 d of lactation were significantly higher in cows fed the anionic diet. Secretion of parathyroid hormone in response to developing hypocalcemia was similar in cows fed either diet. Plasma hydroxyproline concentration (an index of bone Ca resorption activity) was greater in cows fed the anionic diet, suggesting better utilization of bone Ca. Plasma 1,25-dihydroxyvitamin D concentration was correlated inversely with plasma Ca and related directly to …