Cholinesterase-inhibiting (ChE-I) pesticides, which include both organophosphates (OP's) and carbamates, together constitute a very significant proportion of pesticides used in the U.S. and worldwide. ChE-I pesticides are known to disrupt nervous system functioning in animals and humans, and OP's are implicated in human poisonings more often than any other class of pesticides. The U.S. Environmental Protection Agency (EPA) uses ChE-I to characterize the risks of these pesticides since ChE-I is a sensitive predictor of exposure. Assessing the risks of OP's and carbamates on the basis of ChE-I involves many uncertainties. The decisions and assumptions made to resolve these uncertainties are science policy decisions, and can have a significant impact on the final characterization of the risk. This report identifies the principal uncertainties throughout each of the four stages of risk assessment (as described by the National Research Council), discusses the nature and public health implications of these uncertainties, suggests an approach for describing and resolving uncertainties, and provides recommendations useful in developing a science policy for ChEI pesticides. It is concluded that the EPA's use of an uncertainty factor as small as ten is not justified by the available scientific evidence.