The performance of anaerobic hybrid reactors treating an organic solvent-containing synthetic pharmaceutical wastewater was evaluated under various wastewater volumetric loading rates and influent compositional changes. The biodegradation, toxicity and treatability of the target C-3 and C-4 solvents, tert-butanol isopropanol, isobutanol sec-butanol and ethyl acetate, were examined. At a hydraulic retention time (HRT) of 2 days and volumetric loading rates ranging from 3.5 to 4.5 kg COD m(-3) day(-1), the reactors achieved total and soluble COD removal efficiencies of 97-99% in less than five times the HRT. These removal rates were achieved following the introduction of target solvents not previously supplied to the reactors. However, inadequate removal of tert-butanol resulted in a decrease in the soluble COD removal efficiency to 58%. Bacterial enrichments from the reactor biomass using tert-butanol as the sole substrate proved unsuccessful, confirming that tert-butanol is poorly degradable anaerobically. Inclusion of a trace metal cocktail in the feed did not affect steady-state reactor performance, but was beneficial during changes in the influent composition. After 405 days of operation, the matrix-associated biomass contributed only a minor fraction (2-4%) of the total biomass present in both reactors. On takedown, the retained biomass present in the matrix-free section of both reactors was found to be granular in nature, despite the omission of trace elements from the influent to one of the AHRs. The specific methanogenic activity profile of the granular sludge from the trace element limited AHR was, however, significantly lower (alpha = 0.05) than that of the reference AHR.