Development of early defects in diabetic neuropathy has been linked to metabolic abnormalities and is considered reversible. To further address some of the questions concerning the contribution by metabolic derangements to the development of neural defects and reversibility, we have developed an animal model, by feeding rats a diet containing 20% L-fucose, that develops neural defects similar to those that occur in streptozotocin-induced diabetic rats. After 6 weeks on a 20% L-fucose diet, myo-inositol content and Na+/K+ adenosine triphosphatase (ATPase) activity of the sciatic nerve were significantly reduced, as was the motor nerve conduction velocity (MNCV). L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but is increased in diabetic patients. In cultured cells, L-fucose, at concentrations that occur in diabetic circulation, is a competitive inhibitor of myo-inositol uptake. The purpose of the present study was to compare the sequential pattern of the reversibility of the slowing of MNCV with ouabain-inhibited sciatic nerve Na+/K+ ATPase activity and myo-inositol content in rats fed a diet containing 20% L-fucose for a period of 6 weeks followed by a normal diet lasting up to 2 weeks. Unbound L-fucose levels in the serum returned to normal in less than 24 hours of the rats being placed on the normal diet. Normalization of slowed MNCV after removing L-fucose-fed rats from the L-fucose diet followed a pattern of recovery similar to the recovery of sciatic nerve ouabain-inhibited Na+/K+ ATPase activity, with complete recovery occurring within 7 days of the rats being placed on the normal diet. In contrast, myo-inositol content of the sciatic nerve remained decreased following 3 days on the normal diet, and required 14 days for complete normalization. Results from these studies suggest that a causal relationship may exist for reduced Na+/K+ ATPase activity and MNCV in L-fucose-fed rats, and that a measurable decrease in myo-inositol content may not be necessary for the development of these defects in the sciatic nerve.