Objectives: Experimental and in vitro evidences have established that reactive oxygen species (ROS) generated by vascular wall cells play a key role in atherogenesis. Here, we evaluated the rate of ROS generation by testing peripheral monocytes in naive hyperlipidemic subjects. Design and methods: Primary hypercholesterolemic, combined hyperlipidemic, and normopilidemic individuals were studied. ROS generation and the mitochondrial electrical transmembrane potential were estimated by flow cytometry. Plasma oxidized (ox) LDL levels and lipid profile were measured by ELISA and enzymatic colorimetric methods. Results: Both hyperlipidemic groups presented significantly higher rates of monocyte ROS generation and elevated plasma levels of ox-LDL. Combined hyperlipidemic subjects presented increased levels of small dense LDL and insulin. Significant positive correlations between monocyte ROS generation and ox-LDL concentrations were found in pooled data. Conclusions: These data provide evidence that ROS production by circulating monocytes from hyperlipidemic subjects may contribute to the systemic oxidative stress and possibly to atherogenesis. (C) 2009 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.