Abstract: Spiramycin (SP) and amoxicillin (AM) were selected as target antibiotics. The influences of binary mixtures of the two target antibiotics on algal growth, synthesis of Chla, production and release of target microcystins (MCs), MC-LR, MC-RR and MC-YR in Microcystis aeruginosa were investigated. When SP and AM were mixed according to the ratio of their EC₅₀ values (ρ(SP)∶ρ(AM)=1∶7), the algal growth rate and the amount of Chla decreased negatively correlated with the test concentrations after seven-day exposure to 4-15 μg/L of mixed antibiotics. The highest inhibition percentage of 109.86% was observed when treated with a mixture concentration of 15 μg/L. When SP and AM were mixed at equivalent ratio (ρ(SP)∶ρ(AM)=1∶1), the algal growth was stimulated at low concentrations of mixed antibiotics (ρ(SP+AM)≤4 μg/L). The highest growth rate was observed at mixture concentration of 1 μg/L, which was 39.13% higher compared with the control group. However, the algal growth was inhibited at the higher test concentrations (ρ(SP+AM)≥5 μg/L). The synthesis of Chla was inhibited at all test concentrations and all mixed ratios. The mixture of SP and AM showed antagonistic interaction. Furthermore, the mixed antibiotics induced an increase of production and release of target MCs. The highest proportion of extracellular MCs, up to 37.96%, was observed in 5 μg/L of mixed antibiotic-treated group at ratio of ρ(SP)∶ρ(AM)=1∶7. Therefore, the existence of mixed antibiotics would lead to increasing threats of M. aeruginosa to the aquatic environment.