Microcystin-LR (MCLR) and copper are commonly found in eutrophic water bodies because of eutrophic run-offs, cyanobacterial blooms, and copper algicide applications. However, the ecotoxicological risk of their combination remains unknown. This study investigated the effect of MCLR, Cu, and their mixture on the growth and physiological responses of Vallisneria natans. Results showed that the combined toxicity of them was concentration dependent. Synergistic effects were elicited at low concentrations of MCLR and Cu exposure (<= 0.25 +0.64 mg/L). Additive or antagonistic effects were induced at higher concentrations. Single and combined exposures could induce oxidative stress, such as increased superoxide anion radical levels. To cope with oxidative stress, V. natans could activate their antioxidant defense systems, such as enhanced superoxide dismutase production and changes in peroxidase activities. Exposure to combined MCLR and Cu (even only with 0.005 + 0.041 mg/L) adversely affected their antioxidant defense systems. As a consequence, malondialdehyde levels significantly increased. The interaction of MCLR and Cu could also significantly increase the bioaccumulations of MCLR and Cu. This increase could be accounted for their synergistic toxic effects on V. natans. Our results suggested that the exacerbated ecological hazard of MCLR and Cu with environmental concentrations may harm aquatic ecosystems. (C) 2017 Elsevier B.V. All rights reserved.