It has been suggested that cerebral adaptation may occur in response to short-term hypoglycemia. This was examined in the present study by measuring serial changes in cognitive function and symptoms after 60 min of continuous hypoglycemia. Hypoglycemia was induced with a hyperinsulinemic glucose clamp on two separate occasions in 24 non-diabetic human subjects. Cognitive function was assessed using the following cognitive test battery: Paced Auditory Serial Addition Test (PASAT), Rapid Visual Information Processing (RVIP), Trail-Making B (TMB), Digit Symbol Substitution Test (DSST) and Four Choice Reaction Time (CRT). In condition A the blood glucose was maintained at 4.5 mmol/l throughout. On two separate occasions (condition B and condition C) the blood glucose was stabilised at 4.5 mmol/l for 30 min, lowered to 2.5 mmol/l for 60 min and restored to 4.5 mmol/l for 30 min. In each condition the cognitive test battery was performed immediately after stabilisation of blood glucose at 4.5 mmol/l and the subsequent battery was repeated at different time intervals: condition A--after a further 40 min of euglycemia; condition B--after 5 min of hypoglycemia; condition C--after 40 min of hypoglycemia. Acute hypoglycemia induced a significant deterioration in cognitive function which was manifest in all tests except TMB (P < 0.05), but performance ability did not differ between conditions B and C. Symptom scores, assessed by a scaled questionnaire, increased significantly during hypoglycemia (P < 0.001) but no differences were detected between the scores at 30 min and 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)