There is circumstantial evidence implicating hypoglycaemia in the sudden overnight death of young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM), the mechanism of which is unknown. We have investigated the effects of hypoglycaemia on the electrocardiogram in 15 patients with diabetes (8 with IDDM and 7 with NIDDM) using a high resolution computer-based system. Patients were randomized to either 2 h of euglycaemia or hypoglycaemia (at around 3 mmol l -1 ) during the afternoon, using hyperinsulinaemic glucose clamps, the two visits separated by a period of at least 4 weeks. Corrected QT interval (QTc), plasma potassium, and adrenaline were measured at baseline and at 0, 60, and 120 min. The degree of QTc lengthening (from baseline) during clamped hypoglycaemia was greater compared to the euglycaemic control period in patients with IDDM (medianΝrangeΝ at 60 min, 156Ν8 to 258Ν vs 6Ν-3 to 28Ν ms, pΟ½0.02) and NIDDM (120 min, 128Ν16 to 166Ν vs 4Ν-3 to 169Ν ms, pΟ½0.05). The fall in plasma potassium was greater during clamped hypoglycaemia compared to euglycaemia in those with NIDDM (pΟ½0.03) but not in those with IDDM (pΟΎ0.06). The rise in plasma adrenaline was greater during clamped hypoglycaemia in both groups (IDDM pΟ½0.02, NIDDM pΟ½0.02) and there was a strong relationship between the rise in adrenaline and increase in QTc (r = 0.73, pΟ½0.0001). These data demonstrate alteration of ventricular repolarization with lengthening of the QT interval during hypoglycaemia and suggest a possible mechanism by which hypoglycaemia could cause ventricular arrhythmias.