A general procedure has been developed for the concentration/fractionation of mutagenic residue organics from small, <50L, and large, to 1200L, volumes of drinking water obtained from a variety of sources. This procedure features concentration of the residue organics chromatographically by passage of the water through XAD-2 and XAD-7 resins in specially designed columns, details of which are given. The residue organics are eluted from the resins via organic solvents, followed by solvent removal and subsequent bioassay for mutagenicity. Then the residue organics are fractionated via a coupled bioassay/analytical fractionation method which progressively focuses to the bioactive constituents of the complex mixture of residue organics. In this report, results for the optimal operation and validation of the concentration system are given, using drinking water derived from an industrially polluted river system, a wilderness river system and a major aquifer sytem. The methodologies described in this paper provide a comprehensive approach for the concentration/isolation of residue organics from drinking water for studies to identify biohazardous compounds and to characterize these compounds biologically.