A basic assessment of the mutagenic activity of organic residues from water entails application of the Salmonella test to both the parent residue mixture and to major subfractions obtained by reverse phase and/or normal phase HPLC. Such analyses overcome the presence in particular residue mixtures of components which are antagonistic or toxic for the bioassay. When applied to residues obtained by various procedures, the method reveals a wide range of mutagenic activity among environmental waters, depending upon the source of the water sample, the apparent types of natural and anthropogenic compounds it contains, and the water processing and disinfection procedures used in its treatment. Through combinations of specific mutagenic bioassays plus sequential analytical and preparative HPLC fractionations, the method has been shown to be applicable for the isolation of mutagens from residues of a variety of environmental waters.