Phosphate supplementation during total parenteral nutrition (TPN) is essential to prevent hypophosphatemia but individual phosphate requirements vary. We reviewed 68 courses of TPN in 61 patients to determine the incidence of hypophosphatemia and to identify factors which indicate a need for additional phosphate supplementation. Eight (12%) patients were hypophosphatemic before initiation of TPN. Sixty (88%) patients were normophosphatemic when TPN was initiated and 25 (42%) became hypophosphatemic. Of these 60 patients, 20 (38%) of 52 patients became hypophosphatemic when supplemented with 13.6 mM phosphate/liter or more, whereas five (63%) of eight patients became hypophosphatemic when supplemented with only 6.8 mM phosphate/liter TPN fluid. More hypophosphatemic patients required insulin during TPN (48 vs 26%), were initially hyperglycemic (24 vs 9%), were alcoholic by history (24 vs 11%), had evidence of chronic weight loss (64 vs 46%), and had a history of recent diuretic (40 vs 23%) or antacid therapy (56 vs 43%). Hypophosphatemia occurs frequently after initiation of TPN therapy despite phosphate supplementation. Provision of 13.6 mEq phosphate/liter prevents hypophosphatemia in most patients. However, patients who are hyperglycemic, require insulin during TPN, or have a history of alcoholism, chronic weight loss, or chronic antacid or diuretic therapy may require greater supplementation to prevent the development of hypophosphatemia. Chronically malnourished patients require a slower initial rate of infusion as well.