In November 2005, the Japanese Center for the Validation of Alternative Methods (JaCVAM) was established as a part of the Division of Pharmacology at the National Center for Biological Safety and Research affiliated with Japan's National Institute of Health Sciences (NIHS). JaCVAM facilitates the validation, peer-review, and international harmonization of alternative to animals testing. Key objectives of JaCVAM are: 1) facilitate 3R's(*), prioritizing Reduction and Replacement, and 2) to ensure new test methods are validated, peer reviewed, officially accepted by the regulatory agencies, and made internationally compatible. In this paper, JaCVAM's current activities and future directions are shown in the validation and peer review of alternatives to testing for skin irritation, eye irritation, phototoxicity, skin sensitization, acute toxicity, genotoxicity and endocrine disruptor screening. (*) 3R's for animal testing (Reduction, Refinement, Replacement).