The sympathetic nervous system may contribute to excessive hepatic glucose output in Type 2 (non-insulin dependent) diabetes mellitus and could be implicated in the interrelated problem of hypertension. The aim of these studies was to determine whether subjects with Type 2 diabetes had normal sensitivity (compared with age-and weight-matched non-diabetic subjects) to noradrenaline infusion (60ngkg-i. min-~ for 60 min) and to compare the responses with oral tyramine administration (800 mg), and psychological stress (using competitive computer games). Noradrenaline infusion caused significantly greater plasma glucose (mean increment 2.1+0.4 vs 0.6+0.1mmol/1, p<0.005) and pressor responses (mean systolic increment 21+3 vs 11 + 1 mmHg, p < 0.02) in the diabetic subjects. The excessive glycaemia was due to increased hepatic glucose output rather than reduced glucose disposal. Tyramine administration caused significantly increased hepatic glucose output and plasma glucose levels, but with similar responses in the diabetic and non-diabetic subjects; the pulse and pressor responses were also similar between the groups. The psychological stressor induced significant increases in pulse, blood pressure and non-esterified fatty acid levels in the combined group of subjects (p < 0.01) but did not influence plasma glucose levels in either diabetic or non-diabetic subjects. We conclude that pharmacologically-induced sympathetic nervous stimulation can induce hyperglycaemia. Subjects with uncomplicated Type 2 diabetes have increased sensitivity to exogenous noradrenaline but may not hyperrespond to endogenous sympathetic activation.