Cognitive and psychomotor function, hormonal counterregulation and symptom awareness during severe insulin-induced hypoglycaemia were evaluated in 10 insulin-dependent diabetic patients. The glucose-clamp technique (Biostator) was applied to achieve a stable hypoglycaemic (39 +/- 2 mg/dl) plateau. A battery of 7 neuropsychological tests and a standardized questionnaire assessing hypoglycaemia symptoms were administered during euglycaemia and hypoglycaemia. There was a significant increase in counterregulatory hormone response (cortisol, growth hormone, p less than 0.05). Every patient experienced symptoms during severe hypoglycaemia. Four patients, however, were not aware of this threatening metabolic state. There was a significant performance decrement in all but two neuropsychological tests (Aiming Center I, Aiming Center II, Line Tracing Errors, Reaction Time, p less than 0.01; Digit Symbol, p less than 0.05). Performance of simple motor tasks as well as cognitive tasks requiring complex discrimination deteriorated similarly. Furthermore, the patients' general well-being (subjective condition) worsened considerably. In conclusion, a significant impairment of neuropsychological functions emerged during severe hypoglycaemia in insulin-dependent diabetes mellitus, even in the face of adequate hormonal counterregulation, and did not always coincide with an appropriate patient awareness of the actual metabolic state.