The objective of this study was to investigate whether administration of L-Gln would affect mediators of acute phase response in postparturient dairy cows. Twenty-four multiparous Holstein cows were blocked by the expected day of calving and randomly assigned to 1 of the 3 treatment groups (n = 8/group): 1) i.v. infusion of 10 L of 0.85% NaCl (control), 2) i.v. infusion of 106, or 3) 212 g/d of L-Gln mixed with 10 L of 0.85% NaCl solution; each treatment was given 8 h/d for each of 7 consecutive days starting on d 1 after calving. Blood samples were collected 1 wk before the expected day of parturition as well as on d 0, 7, 14, and 21 after parturition; plasma concentrations of serum amyloid A (SAA), haptoglobin, and lipopolysaccharide-binding protein were measured by ELISA, and alpha(1)-acid glycoprotein was assessed by radial immunodiffusion. Concentrations of SAA, haptoglobin, and alpha(1)-acid glycoprotein increased in control cows after parturition, reaching peak values on d 0 or 7 postpartum (60, 1,093, and 963 mu g/mL, respectively). Cows infused with 106 g/d of L-Gln had greater concentrations of SAA in plasma on d 14 and 21 compared with controls (62.8 vs. 30.2 and 71.1 vs. 34.5 mu g/mL, respectively). Cows infused with 212 g/d of L-Gln had greater concentrations of SAA on d 7 (82.5 vs. 53.9 mu g/mL) and lower concentrations of haptoglobin on d 14 and 21 postpartum compared with controls ( 264 vs. 621 and 175 vs. 587 mu g/mL, respectively). Cows treated with 106 and 212 g/d of L-Gln had greater plasma lipopolysaccharide-binding protein concentrations on d 7 compared with control group (50.0 and 35.6 vs. 10.8 mu g/mL, respectively). There were no treatment differences with respect to milk yield and DM intake during the experimental period. In conclusion, our data indicate that i.v. administration of L-Gln modulated acute phase mediators in dairy cows after parturition and warrants further research into the mechanisms behind these effects.