Six ruminally fistulated midlactating multiparous Holstein cows were used in a double 3×3 Latin square design (35-d periods) to study the effects of lasalocid (LAS) and monensin (MON) supplemented at 24 mg/kg of dry matter on digestion, ruminal fermentation, blood metabolites, and milk production. Cows were blocked according to milk production and fed a red clover silage-based total mixed ration (17.8% crude protein) without supplementation or supplemented with LAS or MON. Daily dry matter intake, milk production, and milk fat and protein concentrations were similar among treatments and averaged 23.5kg, 36.6kg, 3.36%, and 3.38%, respectively. Rumen lipogenic:glucogenic volatile fatty acids and NH3-N concentration were lower, and apparent digestibility of dry matter, organic matter, crude protein, and gross energy were higher with than without ionophore supplementation. Compared with LAS, MON increased concentrations of plasma urea-N and milk urea-N, and excretion of urinary urea-N and total N. Monensin also decreased N retention and tended to reduce plasma concentration of nonessential AA in comparison with LAS. Both ionophores reduced daily fecal excretion of N by 13g compared with the control, but MON increased daily losses of urinary N by 36g compared with LAS. Results from this study suggest that postabsorptive metabolism of N might be altered by the type of ionophore fed.