Abstract Inpatients with amyotrophic lateral sclerosis (ALS) and with other various neuromascular (NM) diseases were compared in their responses to the intravenous glucose tolerance test (GTT), the insulin tolerance test (ITT), and the tolbutamide tolerance test: (TTT). Patients with neuromuscular diseases other than ALS (NM control group) responded for all studies within the normal range. Higher fasting serum lipid levels but no significant differences in fasting serum glucose, insulin, or human growth hormone (HGH) were noted in the ALS group. Lower rates of glucose utilization and higher post-glucose insulin levels during the intravenous GTT were observed in the ALS group. These and similar results from the TTT were interpreted as resistance to endogenous insulin in ALS. The ITT studies showed a similar resistance to exogenous insulin among the ALS patients. There was no relationships among the metabolic abnormalities and clinical state of the ALS patients. These data show that ALS patients have insulin resistance and decreased glucose utilization which cannot be explained purely by muscular dysfunction, other adventitious factors secondary to this motor neuron disease, or pancreatic dysfunction. These metabolic abnormalities associated with ALS are differentiated from those of late-onset diabetes, obesity, inanition, and myotonic dystrophy but not from those of severe depression.