Whole sample toxicity assessment can help identify, diagnose and control impacts in the environment arising from the release of hazardous chemicals in complex mixtures. This role for direct toxicity assessment is considered against a background of increased international activity in the regulation of chemicals and reported improvements in the quality of surface waters in England and Wales. International legislation is largely focussed on the regulatory control of chemicals as individual substances although the majority of substances released to the environment enter in complex mixtures either as point source discharges or diffuse inputs. Whole sample measures of biological effect support the traditional substance by substance approach and provide a diagnostic capability to direct investigation into the likely chemicals or groups of chemicals of concern. Reported improvements in surface water quality in England and Wales are considered in the context of current impacts associated with hazardous substances.