To investigate the role of the autonomic nervous system in changes in blood volume and composition induced by acute hypoglycaemia in man, seven healthy subjects participated in three experiments on separate days: insulin-induced hypoglycaemia with concomitant alpha-adrenoceptor blockade; insulin-induced hypoglycaemia with total autonomic blockade (alpha-adrenoceptor blockade combined with beta-adrenoceptor blockade and atropine); and insulin-induced hypoglycaemia without any autonomic blockade. In the experiments without autonomic blockade the peripheral venous hematocrit increased, plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased. In both experiments with autonomic blockade the increase in venous haematocrit was abolished, yet plasma volume decreased, intravascular albumin content decreased and the transcapillary escape rate of albumin increased in these experiments. Thus, the changes in plasma volume and composition in response to hypoglycaemia are due to the combined actions of adrenaline and of insulin.