A meta-analysis was conducted to examine potential empirical relationships between dietary cation-anion difference (DCAD) (Na + K - Cl) and the response of lactating dairy cows. The database was developed from 12 studies published between 1984 and 1997 that included a total of 17 trials, 69 dietary treatments, and 230 cows. Results indicated that DCAD affected performance of lactating dairy cows. Maximum milk yield and feed intake were reached when DCAD was 34 and 40 meq/100 g of feed dry matter, respectively. Blood pH and HCO3 concentrations increased with DCAD, indicating an improved acid-base balance of lactating dairy cows. Changes in urinary pH and urinary excretion of Na, K, and Cl were consistent with varying DCAD, thus dietary acidity or alkalinity. The effects of DCAD were likely mediated via modification of acid-base status in the cows.