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Two studies were performed to evaluate the effects of dried distillers grains with solubles (DDGS) on the lactational performance of dairy cows. The intent of experiment 1 was to evaluate the effects of feeding increasing concentrations of DDGS on the feed intake and production of Holstein dairy cows. Twenty multiparous Holstein cows averaging 76 ± 24 d in milk and 638 ± 68 kg of body weight were randomly assigned to one of five 4 × 4 Latin squares. During each of the 28-d periods, cows were offered 1 of 4 diets: 1) control, 0% DDGS, 2) 10% DDGS, 3) 20% DDGS, or 4) 30% DDGS. For the treatment diets, DDGS replaced a portion of both forages and concentrates. Dry matter intake increased linearly with increasing concentrations of DDGS (21.4, 22.4, 23.0, and 24.0 ± 0.98 kg/d). Similarly, milk production increased linearly (27.4, 28.5, 29.3, and 30.6 ± 1.44 kg/d). The intent of experiment 2 was to evaluate the effect of feeding DDGS on feed intake, milk production, and excretion of urinary purine derivatives (PD). Excretion of PD was used to estimate the effects on rumen microbial crude protein production. Twenty-one multiparous and 13 primiparous Holstein cows, averaging 178 ± 36 d in milk and 651 ± 65 kg of body weight were randomly assigned to 1 of 2 diets in a 3-period crossover design. Cows were offered 1 of 2 rations during each 21-d period. Dietary treatments were either a control (0% DDGS) or 30% dietary dry matter of DDGS. Dry matter intake increased when feeding DDGS (22.8 vs. 24.1 ± 0.74 kg/d for 0 and 30% DDGS, respectively) but milk production, percentages of milk fat and protein, and the ratio of PD to creatinine were not significantly different between the control and DDGS diets. Results of this study suggest a dairy ration may be formulated to contain as much as 30% of dietary dry matter as DDGS.