Proposition 65 (formally titled The Safe Drinking Water and Toxic Enforcement Act of 1986, and also referred to as Prop 65) is a California law passed by direct voter initiative in 1986 by a 63%–37% vote. Its goals are to protect drinking water sources from toxic substances that cause cancer or birth defects and to reduce or eliminate exposures to those chemicals generally, such as in consumer products, by requiring warnings in advance of those exposures, with the intended goal being that companies choose to reformulate their products without the substances rather than simply providing notice of such substances in their product.

In 1986, political strategists including Tom Hayden and his wife, environmental activist Jane Fonda, thought that an initiative addressing toxic pollutants would bring more left leaning voters to the polls to help Democrat Tom Bradley in his gubernatorial race against incumbent Republican George Deukmejian, who had vetoed several pollution cleanup bills. Hayden and others funded the initiative, and found three environmental attorneys to write it, including David Roe who did not expect it to pass. Voters passed it 2–1, but did not elect Bradley.

The act states: "no person in the course of doing business shall knowingly discharge or release a chemical known to the state to cause cancer or reproductive toxicity into water" or into anywhere that feeds a drinking water source. It also says that "no person in the course of doing business shall knowingly and intentionally expose" anyone to those chemicals "without first giving clear and reasonable warning."

Proposition 65 is administered by CalEPA's California Office of Environmental Health Hazard Assessment (OEHHA). Proposition 65 regulates substances officially listed by California as causing cancer or birth defects or other reproductive harm, in two ways. The first statutory requirement of Proposition 65 prohibits businesses from knowingly discharging listed substances into drinking water sources, or onto land where the substances can pass into drinking water sources. The second prohibits businesses from knowingly exposing individuals to listed substances without providing a clear and reasonable warning. The requirements apply to amounts above what would present a 1-in-100,000 risk of cancer assuming lifetime exposure (for carcinogens), or above one thousandth (1/1000) of the no observable effect level (for reproductive toxins).

An official list of substances covered by Proposition 65 is maintained and made publicly available. Chemicals are added to or removed from the official list based on California's analysis of current scientific information. All substances listed show their known risk factors, a unique CAS chemical classification number, the date they were listed, and, if so, whether they have been delisted. As a result of lawsuits, the list now also contains substances known only to cause cancer in animals, and as of 2020,^[update] contains over 900 substances.

Proposition 65 has had limited success in reducing exposures to known toxic chemicals, especially in consumer products, and its successes illustrate gaps in the effectiveness of federal toxics laws (see § Accomplishments below). It remains politically controversial even after more than 30 years (see § Controversy and abuse below), in large part because it, in effect, requires businesses to know the scientific safety level for specific cancer- and birth defect-causing chemicals that those businesses are intentionally exposing members of the public to, unless government has already set those levels. According to the California Environmental Protection Agency, "Proposition 65 has... increased public awareness about the adverse effects of exposures to listed chemicals.... [and] provided an incentive for manufacturers to remove listed chemicals from their products.... Although Proposition 65 has benefited Californians, it has come at a cost for companies doing business in the state."

Enforcement is carried out through civil lawsuits against Proposition 65 violators. These lawsuits may be brought by the California Attorney General, any district attorney, or certain city attorneys (those in cities with a population exceeding 750,000). Lawsuits may also be brought by private parties "acting in the public interest," but only after providing notice of the alleged violation to the Attorney General, the appropriate district attorney and city attorney, and the business accused of the violation.

A Proposition 65 Notice of Violation must provide adequate information to allow the recipient to assess the nature of the alleged violation. A notice must comply with the information and procedural requirements specified in regulations. A private party may not pursue an enforcement action directly under Proposition 65 if one of the government officials noted above initiates an action within sixty days of the notice. After 2003, private enforcers must also serve a certificate of merit (statement of expert consultation(s) supporting belief of reasonable and meritorious private action) as a means of preventing frivolous enforcement actions.