Methylmalonic acidemia is a heterogeneous inborn error of propionate metabolism. Therapy frequently includes a low-protein diet to minimize precursors of methylmalonic acid (MMA) and reduce its concentration in body tissues. Renal dysfunction in these patients is increasingly recognized. Tubulointerstitial disease has been found in the small number of renal biopsy specimens from young children previously reported by others. We describe an 18-year-old patient with the mut- form of the disease who developed renal dysfunction despite the use of a low-protein diet. Tubulointerstitial injury was documented by renal biopsy. The patient had no risk factors associated with established causes of chronic tubulointerstitial nephropathy (CTIN). We postulate that methylmalonyl-CoA and/or its precursors (propionyl-CoA, odd-chain fatty acids), may be capable of producing CTIN. We speculate that prevention of renal injury may require lower tissue levels of MMA and its precursors than those required for prevention of ketoacidosis.