This publication summarizes the scientific knowledge base on which principles and methods involved in neurotoxicity risk assessment are based. It is aimed at providing a framework for public health officials, research and regulatory scientists and risk managers on the use and interpretation of neurotoxicity data from human and animal studies and it discusses emerging methodological approaches to studying neurotoxicity. The introductory chapter examines definitions and critical concepts in neurotoxicity and looks at the criteria for quality of data used in risk assessment. This is followed by a detailed discussion of the structure and function of the nervous system, of the special susceptibilities of the human fetus, children and the elderly and of the types of effects on the nervous system. Recent progress in developing validated methods for detecting neurotoxicity in humans is investigated, as is our understanding of the factors that affect the validity and reliability of human neurotoxicological studies. Sources of human data include accidental and occupational exposures, case-studies, clinical evaluations, epidemiological studies, and field and laboratory studies. Standardized neuropsychological tests, validated computer-assisted test batteries, neurophysiological and biochemical tests, and refined imaging techniques have been improved and become well established. The most extensive section reviews data derived from experimental animal models. Batteries of functional tests have been developed, validated and used extensively in neurotoxicological studies. Many different types of behavioural tests have been used to assess chemical-induced changes in sensory, motor and cognitive function, whereas neurophysiological measures have been standardized to assess chemical-induced sensory and motor function. The final chapter examines the steps involved in neurotoxicity risk assessment: hazard identification, dose-response assessment, exposure assessment and risk characterization. The application of risk assessment principles for neurotoxicants is similar to that of other non-cancer end-points, except that issues of reversibility, compensation and recovery of function in the nervous system require special consideration. This document provides guidance on neurotoxicity risk assessment at a broad international level.