1. Recent hypoglycaemia reduces the counter-regulatory and symptomatic response to the next episode of hypoglycaemia. This study was designed to determine whether antecedent hypoglycaemia (a) affected the sympathoadrenal response to other stimuli (postural change and a mathematical stress test, (b) was associated with adaptation of cognitive function and (c) if avoided for 6 days led to the restoration of the counter-regulatory response to hypoglycaemia. 2. On the morning of day 1, 10 healthy men had their response to the sympathoadrenal stimuli assessed before an episode of hypoglycaemia (2.5 mmol/l). A further hyperinsulinaemia clamp was performed for 2h (blood glucose 3.0 mmol/l or 5.0 mmol/l) in the afternoon and the assessments repeated the next day and 6 days later. Cognitive function using the four-choice reaction time test was assessed before and during the episodes of morning hypoglycaemia. The whole study was repeated 4 weeks later with the other afternoon glucose level. 3. Adrenaline levels and sweat rates were reduced (P < 0.05) on day 2 during hypoglycaemia on both occasions and had not returned to normal after 6 days. Symptom scores were lower (P < 0.05) only on day 2 after the afternoon of hypoglycaemia. The responses to the sympathoadrenal stimuli and cognitive function were unaffected by antecedent hypoglycaemia. 4. The adaptation of the counter-regulatory response to antecedent hypoglycaemia appears to be specific to hypoglycaemia. The response takes longer than 6 days but less than 4 weeks to return to normal. Antecedent hypoglycaemia does not lead to cerebral adaptation.