Impaired intestinal integrity caused by excessive hindgut starch fermentation is a potential source of peripheral inflammation in dairy cattle. Study objectives were to evaluate effects of hindgut acidosis in lactating dairy cows. Five rumen-cannulated Holstein (244 ± 49 DIM, 33 ± 3 kg milk/d) cows were enrolled in a study with 2 experimental periods (P) during which cows were fed a diet with 26% starch ad libitum. During P1 (4d), baseline data were collected. During P2 (7d), cows were abomasally infused with 4 kg/d of starch (1 kg pure corn starch + 1.25 L H2O/infusion at 0000, 0600, 1200, and 1800 h). Milk, feces, and blood samples were collected daily. Effects of time were assessed using PROC MIXED (SAS Inst. Inc., Cary, NC). Compared with P1, starch infusion markedly reduced fecal pH (5.98 vs. 6.76; P < 0.01) and increased fecal starch content (3-fold; P = 0.01). Milk yield and DMI were reduced by starch infusion (4 and 5%, respectively; P < 0.05). Rectal temperature remained unchanged following infusions. Milk urea nitrogen decreased (10%; P < 0.01) relative to P1; however, starch infusions did not affect milk fat, protein or lactose content. Milk SCC increased 11-fold (P = 0.05) during P2. Circulating insulin and β-hydroxybutyrate increased (141 and 53%, respectively; P < 0.01), while plasma glucose tended to decrease (9%; P = 0.06) at 14h relative to the first infusion (RFI). Starch infusion increased blood urea nitrogen 2h RFI (22%) before it promptly decreased (12%; P = 0.03) for the remainder of P2. Additionally, P2 NEFA concentrations decreased (32%; P < 0.01) relative to P1. Monocytes decreased (38%; P = 0.03) at 2h RFI, but there were only minor increases in white blood cells, neutrophils, lymphocytes, eosinophils and basophils relative to P1 (10, 13, 7, 30, and 20%, respectively; P < 0.05). Circulating serum amyloid A and lipopolysaccharide binding protein concentrations were unaffected by starch infusion. Although abomasal starch infusion markedly reduced fecal pH and altered bioenergetics, it only had minor effects on metabolism, inflammation, and production in cows consuming a moderately high starch diet.