To investigate the effect of gender on catecholamine responses to hypoglycaemia, single-step euglycaemic-hypoglycaemic clamps have been performed in 14 healthy men and 17 women. Adrenaline responses were 44% lower in females (p<0.01) and noradrenaline 17% lower (p=0.08). In response to low-dose intravenous insulin infusion (0.3 mU · kg⁻¹ · min⁻¹), plasma glucose fall and counter-regulation in seven men and seven women had a different course (p<0.001), with different glucose kinetics. In men, endogenous glucose output recovered quickly to levels that exceeded basal; in women suppression of endogenous glucose output was more prolonged, without rates ever exceeding basal (p<0.05). Peripheral glucose uptake was stimulated in men only. The hormones of acute glucose counter-regulation (catecholamines and glucagon) did not differ between the sexes during this challenge, the catecholamine response in the women being supported by the continuous fall in plasma glucose. These results suggest that: 1) catecholamine responses to moderately controlled hypoglycaemia are diminished in women, and 2) Peripheral insulin sensitivity in men is enhanced over that of women but hepatic sensitivity to insulin may be greater in women.