Detection of contractile reserve is important in heart failure patients. To determine if detection of contractile reserve is influenced by neuroadrenergic activation, we examined the relation between dobutamine stress echocardiography (DSE) findings and plasma norepinephrine levels (NE) at rest in 35 patients with nonischemic left ventricular (LV) dysfunction (New York Heart Association class >III in all; LV ejection fraction 0.27 +/- 0.5). Changes in global wall motion score (WMS), and separately in WMS of hypokinetic segments and akinetic segments, were analyzed. A patient was considered to be responsive to dobutamine if the change in global WMS was >/=4. Twenty-three patients were responsive and 12 were not responsive to dobutamine. Plasma NE and baseline heart rate were significantly higher in nonresponsive patients (p <0.001). Changes in global WMS and in hypokinetic segment WMS were inversely related to either plasma NE (r -0.68 and -0.67, respectively) or baseline heart rate (r -0.60 and -0.66, respectively). The change in akinetic segment WMS was related to plasma NE only (r -0.50). Changes in WMS were not related to age, diastolic and systolic LV volume, baseline global WMS, or number of akinetic segments at baseline. Plasma NE >602 pg/ml predicted a blunted or absent contractile reserve at DSE (sensitivity 92%; specificity 87%). Neuroadrenergic activation may influence contractile reserve found at DSE in patients with heart failure due to nonischemic LV dysfunction.