Diets offered to lactating dairy cows in the pasture-based dairy systems in southeastern Australia can vary in their dietary cation-anion difference (DCAD) from 0 to +76 mEq/100 g. The effects of such a range of DCAD on the health and production of cows, on a predominantly pasture-based diet, were examined in an indoor feeding experiment. Four groups of five cows were offered a diet of 5 kg of barley and ad libitum pasture, which is a diet representative of what is offered to cows in early lactation in the region. The cows were supplemented twice daily, with varying levels of salt combinations to alter the DCAD, which ranged from +21 to +127 mEq/100 g. Although a reduction in DCAD to +21 mEq/100 g caused a nonrespiratory systemic acidosis, there was a threshold value, above which blood and urine pH did not appear affected, although the strong ion difference of blood and urine and the blood bicarbonate concentration increased linearly (P < 0.05, 0.001, and 0.01, respectively). A DCAD above +21 mEq/100 g linearly reduced dry matter intake (P < 0.1), average daily bodyweight gain (P < 0.05), and milk protein yield (P < 0.05) but did not have a significant effect on the concentration of fat, protein, or lactose in milk. Although data were consistent with a tendency for milk yield to decrease as dietary cation-anion differences increased, this trend was not statistically significant. Urine hydroxyproline to creatinine ratio increased (P < 0.001) as dietary cation-anion difference increased, possibly suggesting an increased rate of uterine involution. It is concluded that a range in the dietary cation-anion difference, above +52 mEq/100 g, may have deleterious effects on dry matter intake and milk production.