We reviewed 16,621 blood chemistry samples taken over a 12-week period; 34 patients with severe hypophosphatemia (serum phosphate level less than or equal to 1.0 mg/dl) were identified, for an incidence of 0.24%. The most common causes of severe hypophosphatemia (SH) in this population were infusion of dextrose solutions (73%), nutritional recovery syndrome (50%), phosphate-binding antacids (50%), and alcohol withdrawal (32%). In general, the patients were normophosphatemic at the time of hospitalization, and SH occurred early in the hospital course. All of the patients responded to the drop in serum phosphate by renal conservation of phosphate (Tm PO4/GFR less than 1.0 mg/dl GFR). Patients required small doses of phosphate to achieve a serum level above 2.0 mg/dl, with 50% of the population receiving less than 25 mmol of replacement therapy. Regardless of the route or amount of replacement therapy given, the course of SH was typically short and without sequelae.