The ultimate goal of toxicologic investigations of both natural and man-made fibrous and nonfibrous particles is to provide essential input for the assessment of potential human risks from exposure to these materials. The development of risk assessment procedures for airborne particles has evolved over the years. The earliest assessments for naturally occurring materials used direct human observations and incorporated safety factors to arrive at allowable human exposures. More recently, there has been a need to assess the potential risk associated with production and use of certain man-made materials for which human data are not available or are inadequate. For these materials, it has been necessary to assess human risks using data obtained from studies conducted in laboratory animals and with cells or tissues. During the last several decades, it has been suggested that data on the mechanisms by which particles cause disease could be used to reduce the uncertainty in estimates of human risks of particle exposures. This article provides comments on the use of mechanistic data in the risk assessment process and suggestions for increasing the successful development and use of mechanistic data in risk assessments conducted in the future.