Historically the U.S. Environmental Protection Agency has used mutagenicity information as part of its weight-of-evidence approach to discern the potential for human carcinogenicity. It is clear from the 1986 Mutagenicity Risk Assessment Guidelines that the USEPA intends to regulate chemicals based on risk of an adverse heritable effect in human germ cells. These Guidelines present a weight-of-evidence scheme for determining if an agent may be a potential human mutagen. Emphasis is placed upon a chemical's intrinsic mutagenic potential, its ability to reach the gonad and interact with germ cell DNA, and its ability to induce heritable mutations in mammalian species. The document summarizes the requirements for mutagenicity testing for submission of data to the USEPA's Office of Pesticide Programs and the Office of Toxic Substances. The rationale and support for the revised guidelines is presented and questions about the revision process and the guidelines themselves are addressed.