The use of short-term bioassay tests in conjunction with analytical measurements, constitute a powerful tool for identifying important environmental contaminants. The authors have coined the terminology 'bioassay directed chemical analysis' to best describe this marriage of analytical chemistry and biology. The objective of this methodology is to identify key compounds in various types of air pollutant samples. Once that task is completed, studies on metabolism, sources, environmental exposure and atmospheric chemistry can be undertaken. The principles and methodologies for 'bioassay directed chemical analysis' are presented and illustrated in this paper. Most of this work has been directed toward the characterization of ambient air and diesel particulates which we will use as examples in this report to illustrate the analytical logic used for identifying the bio-active components of complex mixtures.