BACKGROUND: This study involved model evaluation of the acute impact of erythromycin on substrate utilization of aerobic activated sludge biomass, at sludge ages of 10 and 2 days. Acute inhibition experiments involved two fill/draw reactors, supplying the biomass, and two sets of batch reactors, which were all fed with the same peptone-meat extract mixture. Each set included a control reactor started without antibiotic addition and parallel reactors with pulse erythromycin additions. RESULTS: Model evaluation of the oxygen uptake rate, chemical oxygen demand and intracellular storage profiles indicated that erythromycin did not affect microbial growth. However, it totally stopped substrate storage and accelerated endogenous respiration. Enhanced endogenous respiration could be explained by higher maintenance energy required for generating specific inactivating enzymes to prevent the toxic effects of erythromycin. CONCLUSION: Major impact was partial obstruction/binding of available substrate for microbial utilization, suggesting uncompetitive inhibition. The present study is unique in emphasizing the increase in maintenance-energy requirements of microbial cultures upon erythromycin exposure, by respirometric and modeling approaches. (C) 2013 Society of Chemical Industry