Phlorizin is known to increase whole-body glucose demand, but it has also stimulated lipolysis in past studies in ruminants. Increased lipolysis complicates studies of dry matter intake (DMI) regulation by hepatic oxidation by providing the liver with additional oxidative substrate. Therefore, to assess whether increased glucose demand selectively increases DMI for cows in negative energy balance, phlorizin was administered to early- and late-lactation cows. Six Holstein cows in early lactation (19 +/- 6 DIM, 50.0 +/- 1.8 kg/d of milk, mean +/- SD) and 6 Holstein cows in late lactation (228 +/- 18 DIM, 30.6 +/- 1.9 kg/d of milk) were randomly assigned to treatment sequence in a crossover design. Periods were 14 d with 7-d adaptation periods and 7 d of treatment. Phlorizin (4 g/d) and propylene glycol (carrier and control) were administered subcutaneously every 6 h throughout the treatment periods. Feeding behavior and DMI data were collected for the final 4 d of each treatment period; blood samples and total urine output were collected on d 4 of each treatment period. Phlorizin caused urinary loss of glucose at 333 g/d in early-lactation cows and 532 g/d in late-lactation cows. Phlorizin increased plasma nonesterified fatty acid concentrations similarly in early- and late-lactation cows, but did not significantly alter plasma insulin concentrations. Treatment with phlorizin tended to decrease meal size, but also decreased intermeal interval, resulting in no effect on DMI. The effects of phlorizin on lipolysis, feeding behavior, and DMI are not dependent on relative energy balance.