In 1990, the senior management of the US Environmental Protection Agency, Office of Pesticide Programs and Toxic Substances (now called the Office of Prevention, Pesticides and Toxic Substances, or OPPTS) directed the two offices forming OPPTS to “harmonize” their human health, environmental/ecological effects, environmental fate, and physical chemistry testing methods into a single set of test guidelines. These two offices, the Office of Toxic Substances, now the Office of Pollution Prevention and Toxics (OPPT) and the Office of Pesticide Programs (OPP), assess risks posed by industrial chemicals and pesticides, respectively. Each office had developed separate testing guidance and methods. Under the Toxic Substances Control Act of 1976, OPPT developed and published an extensive set of environmental effects test guidelines and technical support documents on testing requirements. In a similar manner, OPP published data requirements for registration of pesticides and developed Standard Evaluation Procedures (SEPs) to explain the procedures used to evaluate submitted ecological effects data. Harmonization of OPPT and OPP guidelines is advantageous because it avoids unnecessary testing, conserves resources, and avoids duplicative testing of chemicals being reviewed by more than one office. Also, there is better coordination of test reviews between each office and greater consistency in test interpretation. Harmonization results in increased guideline uniformity between offices, and a more efficient means of revising and updating the OPPTS guidelines. The Organization for Economic Cooperation and Development (OECD) was similarly engaged in guideline development in the 1970s, and published a set of biotic effects test guidelines in 1981 (second addendum was published in 1984). EPA intends to harmonize OPPTS guidelines with those of the OECD to avoid unnecessary testing of chemicals in international commerce, increase efficiency in reviewing chemicals, use fewer test animals, and reduce nontariff trade barriers. Efforts to date by OPPTS have resulted in developing drafts of ecological effects test guidelines (the “850” harmonized guidelines). These were available as public drafts in 1996; the OPP Scientific Advisory Panel commented on them at that time. Currently the guidelines are being revised and will be available as part 850 in volume 40 of the US Code of Federal Regulations. Examples are discussed of how the harmonized test guideline process between OPPTS and OECD operates and the progress achieved to date. These include development of a revised OECD daphnid chronic test, a new harmonized fish early life stage test, a new OECD aquatic macrophyte toxicity test (Lemna [duckweed] growth inhibition test), and OECD activities in chironomid sediment testing and terrestrial plant toxicity testing. Important harmonization limitations, possible problems, challenges, and future activities are discussed.