The objectives were to model empirical interrelationships among dietary macromineral elements and cation-anion difference influencing DMI, milk yield, 4% FCM yield, and milk composition of dairy cows. The database consisted of 1022 cow-period means collected from 326 midlactation cows in experiments with incomplete block designs. Dietary concentrations of elements ranged from below to above current recommendations, and cation-anion difference (Na + K-Cl) was from +5.8 to +61.2 meq/100 g of dietary DM. Interrelationships were detected for dietary concentrations of Na by K for DMI, 4% FCM yield, and milk fat percentage; Na by Ca for DMI, milk yield, and 4% FCM yield; K by Cl for DMI, 4% FCM yield, and milk protein percentage; K by Ca for 4% FCM yield, milk protein, and fat percentages; Na and P for DMI and milk protein percentage; and K by P for 4% FCM yield and milk fat percentage. Maximal DMI and milk yield were observed with .58% Na, .40% Mg, and +38 meq/100 g of dietary DM. Agreement was close for DMI and milk yield responses to dietary cation-anion difference from our database and independent data sets. The models developed are empirical, do not necessarily establish cause and effect, and should be evaluated prudently; however, they provide useful information to design future research.