This study examined the effects of prolonged hyperglycemia on renal handling of glucose and explored the in vivo pharmacological effects of phlorizin on glucose transport in the rainbow trout. The transport of glucose was examined by experimentally elevating the rate of renal glucose reabsorption via infusion of the fish with exogenous glucose at a rate of 70 μmol kg–1 h–1 and by inactivating the glucose transporters via the simultaneous administration of phlorizin (1 μmol kg–1h–1). Glucose was reabsorbed against a concentration gradient, until plasma glucose levels reached ∼22 μmol l–1 and the transport maximum of glucose in the kidney(∼145 μmol kg–1 h–1) was exceeded. At this point, glucose was lost to the urine, resulting in glucosuria. Glucosuria affected water reabsorption, approximately doubling the water clearance ratio,and resulted in osmotic diuresis. This in turn reduced Na+reabsorption, increasing the amount lost to the urine from 0.5% to 2% of the filtered load. Glucose reabsorption was found to be correlated with Na+ reabsorption, though the latter was almost 10-fold higher than glucose transport rates. Phlorizin treatment reduced glucose reabsorption,although it did not block it entirely until 48–72 h of infusion. The glucosuria resulting from the blockade of the glucose transporters resulted in a similar osmotic diuresis and a greater Na+ loss to the urine (9%of filtered load). The results are discussed with respect to the net renal`wasting' of glucose and the detrimental osmoregulatory and ionoregulatory effects associated with glucosuria caused by carbohydrate-rich diets.