To evaluate the role of hyperglycemia and excessive polyol pathway activity in the pathogenesis of nerve disorders in diabetes, motor nerve conduction velocity (MNCV) was measured in dogs alloxan diabetic or experimentally galactosemic for 5 years. Diabetic dogs in poor glycemic control showed a progressive decline of MNCV from baseline values. Diabetic dogs that had been randomly assigned to good glycemic control retained normal MNCV. Nondiabetic dogs made galactosemic by a 30% galactose diet developed erythrocyte polyol concentrations many-fold greater than in diabetic animals, but the MNCV remained unchanged and comparable to that of normal dogs. Nerve polyol levels, when compared in short-term diabetic dogs or dogs galactose-fed 2 to 4 months, were elevated at least as much by the galactose-rich diet as by diabetes. Thus, in dogs, excessive tissue polyol accumulation is associated with subnormal MNCV in diabetes, but not in experimental galactosemia.