Reactive oxygen species (ROS) have been implicated in the aetiology of several pathological and degenerative diseases. The protective effect of natural products possessing antioxidant properties has played a crucial role in ameliorating these deleterious effects. This study investigated the chemoprotective properties of the methanolic extract of Vernonia amygdalina (MEVA) in an experimental model of tert-butyl hydroperoxide (t-BHP)-induced human erythrocyte lysis in vitro. Haemolysis was induced by incubating erythrocytes with t-BHP (2 and 3mM) in vitro. Samples of erythrocyte suspensions were removed at different intervals over a 6-h period, and the degree of haemolysis was measured. The anti-haemolytic effect of MEVA at 25-150 mu gml(-1) concentrations on the samples were assessed and compared with Triton X-100. Administration of t-BHP at 2- and 3-mM concentrations significantly (p<0.05) induced erythrocyte lysis by 37.5% and 31.4%, respectively. The addition of MEVA, however, reduced t-BHP-induced erythrocyte lysis significantly (p<0.05) by 39.3%, 48.4%, 67.3% and 73.4% at 25, 50, 100 and 150 mu gml(-1) concentrations, respectively. MEVA likewise protected against t-BHP-induced lipid peroxidation significantly (p<0.05) at 100 and 150 mu gml(-1) by the fourthhour and non-significantly (p>0.05) at all concentrations by the sixth hour. The reduced glutathione level was, however, increased with the administration of t-BHP, while a delayed addition of MEVA had no protective effect on the t-BHP-induced cell lysis. These findings therefore suggest that MEVA may have protective antioxidant properties, making it suitable for incorporation into food and drug products. Copyright (c) 2012 John Wiley & Sons, Ltd.