purpose: To investigate hypoglycemic and hyperglycemic symptoms, accuracy of estimating blood glucose, and their relation to glycemic control and counterregulatory hormone levels in insulin-dependent diabetes mellitus.patients and methods: During randomly ordered stepped hypoglycemic and hyperglycemic insulin clamps on two separate days, 42 patients with insulin-dependent diabetes mellitus rated the intensity of 40 moods and symptoms when glucose was 8.9, 5.6 and 2.2 mmol/L, and 8.9, 14.4 and 21.1 mmol/L. The subjects were blinded to their actual glucose levels and asked to estimate them at each step. Epinephrine, norepinephrine, cortisol, growth hormone, and glucagon were measured at each glucose plateau.results: Cluster analysis yielded five symptom groups during hypoglycemia: autonomic symptoms, negative moods, positive moods, feeling weak/dizzy, and feeling relaxed. At 2.2 mmol/L, mean scores for all five symptom groups and 11 of 17 unclustered symptoms differed from those reported at the baseline glucose of 8.9 mmol/L (P =<0.05), but 34% of patients reported no awareness of autonomic symptoms. The intensity of autonomic symptoms correlated positively with HbA 1 (r = .43, P <0.01), epinephrine (r = .59, P <0.001), norepinephrine (r = .45, P <0.01) and cortisol (r = .62, P < 0.001), and negatively with glucose estimation error (r = -.45, P = 0.01). Six patients (15%) were unaware of both autonomic and neuroglycopenic symptoms during hypoglycemia. At 21.1 mmol/L, only 5 of 40 symptoms differed (P <0.05) from baseline. Seventeen percent of subjects made potentially serious errors when estimating glucose at 2.2 mmol/L, and 66% at 21.1 mmol/L. Many patients experienced symptoms different from those they reported as their usual manifestations of changing glucose levels.conclusions: Since the majority of patients made clinically serious errors in glucose estimation, and many used symptoms that did not discriminate hyperglycemia and hypoglycemia, individualized training to increase awareness of glucose-related symptoms and glucose levels may help patients reduce the frequency or severity of hyperglycemic and hypoglycemic events.