The influence of nitrogen on the effects of the antibiotic contaminant spiramycin on Microcystis aeruginosa was studied through a 7-day exposure test. At current contamination levels of 0.5-100 mg L-1 for nitrogen and 0.1-0.4 mu g L-1 for spiramycin, the two factors significantly interacted with each other (p < 0.05) on the synthesis of chlorophyll-a and protein, the production and release of microcystins as well as the expression of ntcA gene and mcyB gene in M. aeruginosa. Nitrogen significantly affected the toxicity of spiramycin on algal growth (p < 0.05) via regulation of protein synthesis. The photosynthesis system including chlorophyll-a, the psbA gene, and the rbcL gene participated in stress responses to spiramycin. Coexisting spiramycin contaminant increased the harm of M. aeruginosa by stimulating the production and release of MCs at a nitrogen level of 0.5 mg L-1, but alleviated M. aeruginosa pollution at higher nitrogen levels of 5-100 mg L-1 by inhibiting algal growth, the production of microcystins and the expression of ntcA and mcyB. The nitrogen-dependent effects of spiramycin should be considered in the control of M. aeruginosa bloom in the presence of spiramycin. (C) 2014 Elsevier B.V. All rights reserved.