Changes of biodegradability and toxicity were followed up on aqueous solutions of sulfamethoxazole (SMX), during ionizing radiation treatment. The biodegradability of SMX (0.1mmoldm−3) was specified by five-day biological oxygen demand (BOD5), using municipal activated sludge, and the results showed an improvement with applying only 0.4kGy dose. BOD5 further increased with prolonged irradiation, indicating a conversion of SMX, a non-biodegradable compound, to biologically treatable substances. At 2.5kGy dose, the BOD5/COD ratio increased from 0 to 0.16. The total organic carbon (TOC) content showed a decrease of only 15% at this point, thus high degree of mineralization is not necessary to make SMX digestible for the low concentrations of microorganisms used during BOD5 measurements. Increment in respiration inhibition of municipal activated sludge was observed with increasing the dose. The EC50 values showed a decrease of one order of magnitude when changing the dose from 0.4kGy to 2.5kGy. The increase of inhibition and formation of H2O2 showed a strong correlation.