Studies of structure-activity relationships and molecular mechanisms of action are fundamental to our understanding of the harmful effects of chemicals on the environment and their more direct effects on human health. It is important to identify factors that determine toxicological effects of foreign chemicals in biological systems and to assess our knowledge about chemical mechanisms of toxicity. Several fundamental mechanisms underlying toxic action are described, and the importance of studying receptor-substrate interactions is stressed. The Ah receptor is cited as an example of a protein-small molecule interaction associated with extreme acute toxicity in laboratory animals. It is recognized that reliable attempts at predictive toxicology across compound classes through structural and theoretical chemistry approaches must be based on sound knowledge about mechanisms of action at the molecular level. Such studies also contribute to the knowledge base in biomedical and physical sciences.