Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.