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Several sites in the United States have groundwater contaminated with mixtures of high explosives and chlorinated solvents. This research examined the ability of two microbial cultures (anaerobic sludge and a facultative enrichment culture) to biodegrade single- and dual-contaminant mixtures of trichloroethene (TCE) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) under anaerobic conditions. In single component batch tests, both cultures degraded 0.6–1 mg RDX/L and its nitroso metabolites to below detection limits in <7 days. During initial 9-day TCE biodegradation tests, the anaerobic sludge did not transform TCE, whereas the facultative culture transformed approximately 10% of the initial 1.4 mg TCE/L. Prior to dual-contaminant batch tests, both cultures were grown in the presence of TCE. Subsequently, both acclimated cultures rapidly biodegraded mixtures of RDX and TCE. Both cultures degraded RDX and RDX-nitroso compounds to below detection limits in <4 days. In the same tests, TCE-acclimated anaerobic sludge converted TCE primarily to cis-dichloroethene (cis-DCE), while the acclimated facultative culture produced cis-DCE and other chlorinated metabolites. These preliminary results demonstrate that anaerobic bioremediation may be part of a feasible groundwater remediation alternative for mixtures of TCE and RDX.