Groundwater contaminated with perchlorate and nitrate was treated in a pilot plant using a commercially available ion exchange (IX) resin. Regenerant brine concentrate from the IX process, containing high perchlorate and nitrate, was treated biologically and the treated brine was reused in IX resin regeneration. The nitrate concentration of the feed water determined the exhaustion lifetime (i.e., regeneration frequency) of the resin; and the regeneration condition was determined by the perchlorate elution profile from the exhausted resin. The biological brine treatment system, using a salt-tolerant perchlorate- and nitrate-reducing culture, was housed in a sequencing batch reactor (SBR). The biological process consistently reduced perchlorate and nitrate concentrations in the spent brine to below the treatment goals of 500μg ClO₄⁻/L and 0.5mg NO₃⁻-N/L determined by equilibrium multicomponent IX modeling. During 20 cycles of regeneration, the system consistently treated the drinking water to below the MCL of nitrate (10mgNO₃⁻-N/L) and the California Department of Health Services (CDHS) notification level of perchlorate (i.e., 6μg/L). A conceptual cost analysis of the IX process estimated that perchlorate and nitrate treatment using the IX process with biological brine treatment to be approximately 20% less expensive than using the conventional IX with brine disposal.