P depletion is often overlooked in the neonate even though acid base management significantly alters P metabolism. Alkalosis is standard treatment for severe PPHN. We report 2 infants with severe PPHN and asymptomatic P depletion during treatment. Case 1: Term girl born to a drug abusing mother, birth wt. was 2.5 kg, Apgar 1 and 3. PPHN was diagnosed on d1 and treated with high frequency ventilation (HFV), and combined resp. and metabolic alkalosis (Na bicarb. and THAM, pH 7.5-7.6, and PCO2 30-40 mmHg). On d3 parenteral nutrition (PN) was started with Ca 0.7 mEq/kg, P 0.45 mM/kg, and Mg 0.5 mEq/kg. On d9, serum P was 0.1mg/dl (N: 4.3-9.3), iCa 1.2mmol/L (N: 1.12-1.23), Mg 1.7 mg/dl (N: 1.4-2). and glucose normal. She was treated with IV KHPO4 bolus providing elemental P 2.5mg/kg over 6 hs. Serum Ca, Mg, and P were monitored and boluses repeated until serum P reached 2.7 (d13). Serum Ca dropped to 5.4 mg/dl (N: 8-11.5) on d15 which responded to increasing Ca in PN to 2 mEq/kg. Infant maintained normal serum P, Mg, and Ca until d18 when she died of resp. failure and PPHN. Case 2: Term girl, birth wt. 3.6 kg, Apgar 2,5, and 6, meconium aspiration. PPHN developed on d1, treated with HFV, and combined resp. and metab. alkalosis. On d2, PN was started, with Ca 1.0 mEq/kg, P 0.6 mM/kg, and Mg 0.6 mEq/kg. Serum P was 1.0mg/dl, iCa 0.82mmol/L, Mg 1.3 mg/dl, and glucose normal. She was treated with slow IV KHPO4 and Ca Gluconate boluses. On d3 serum P, iCa and Mg dropped to 0.7mg/dl, 0.59mmol/L, and 0.5mg/dl. Urine P and Ca were 1.2mg/dl. and 5.9mg/dl respectively. Serum P, iCa, and Mg were monitored every 6 hs and boluses repeated until P reached 2.9mg/dl, iCa 1.3 mg/dl. Serum Mg was high from d3-8 (2.1-2.6 mg/dl). Infant was placed on ECMO, d3-6. Serum P, Ca, and Mg were normal until discharge on d26. Discussion: Acute P flux into intracellular and skeletal pools causes acute hypophosphatemia. Alkalosis, particularly respiratory, stimulates intracellular P uptake. Intracellular diffusibility of CO2 creates acute drop in intracellular pH, and production of phosphorylated metabolites. Excessive renal, or intestinal losses were ruled out as acute drop was rapidly corrected with P supplement and did not recur when pH normalized.Conclusion: In management of PPHN with resp. or metab. alkalosis, monitoring of serum P is necessary to prevent and detect acute P depletion.