Type 1 diabetes mellitus (T1DM) is associated with a peripheral neuropathy that reduces nerve conduction velocity. This may impair high motor-unit discharge frequencies (MUDF), decrease muscle activation, and curtail the ability to sustain repetitive contractile tasks. We examined (1) whether MUDF, the contractile properties of the knee extensors, and the conduction velocity of persons with T1DM differed from controls; (2) whether persons with T1DM can maintain adequate MUDF during a fatigue protocol; and (3) the relationship between these parameters and impaired glycemic control. We studied male and female subjects with T1DM and controls matched for age, height, weight, and gender. Single motor unit recordings were made from vastus lateralis during maximal and submaximal contractions and during a fatigue protocol. Glycemic control was assessed from blood glucose concentration and glycosylated hemoglobin (HbA1c). Control femoral conduction velocities were comparable to literature values and those of the T1DM subjects were slower. These values correlated with plasma glucose and HbA1c. T1DM subjects fatigued 45% sooner than controls, and time to fatigue and conduction velocity were correlated (r = 0.54, P < 0.05). Discharge frequencies tended to be slower during 50% maximal voluntary contractile force in the T1DM subjects at task failure. Persons with T1DM had slower conduction velocities and lower MUDF than their controls, which apparently leads to impaired activation of muscle and decreased endurance during isometric fatigue.