Traditional management of methylmalonic acidemia includes limited whole protein consumption and maintenance of caloric intake with a metabolic formula. Even with a strict diet, methylmalonic acid (MMA) levels remain elevated and patients are at risk for metabolic decompensation with acute illness. This may be due to the fact that branched chain amino acids account for only half of the precursors metabolized by the methylmalonyl pathway. Other precursors include propionate (25%) produced by the large bowel anerobic flora and odd chain fatty acids (25%). Short term metronidazole treatment has been useful in reducing gut flora and limiting propionate production. However, no long term treatment outcome has been reported. We report improvement following metronidazole in a 4 year old male with methylmalonic aciduria (type mut0) which was uncontrolled by conventional therapy. J.L. was diagnosed at age 6 months and dietary modification was instituted. Over the past 15 mos, he has been managed with Propimex and ProPhree formulas. MMA levels ranged from 286 to 526 μmol/L (normal ≤0.40). In Feb '97, J.L. contracted a viral illness, developed ketoacidosis and was treated with IV hydration. However, 24 hrs after discharge, he was readmitted with ketoacidosis. After 4 days of IV fluids and gastrostomy feedings, there was no response and metronidazole was added (150 mg BID=18 mg/kg/day). J.L. readily improved and was discharged 2 days later. Serial MMA levels showed a sustained improvement: 120 μmol/L (on 150 mg BID × 2 wks), 90 μmol/L (on 150 mg/day × 4 wks), and 81 μmol/L (on 75 mg/day × 6 wks). However, after 5 mos MMA levels increased again (to 353 μmol/L), perhaps due to metronidazole resistance. The metronidazole is now being cycled every 3 wks and J.L. has remained clinically stable. This experience with metronidazole suggests anaerobic gut flora have a significant role in the metabolic control of patients with methylmalonic acidemia but long term therapy may not prove as beneficial as suggested by previous short term experiences. Longer follow-up will be required to adequately answer this question.