This paper summarises and extends the work developed over the last decade by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) for acute health risk assessment of agricultural pesticides. The general considerations in setting of acute reference doses (ARfDs) in a step-wise process, as well as specific considerations and guidance regarding selected toxicological endpoints are described in detail. The endpoints selected are based on the practical experience with agricultural pesticides by the JMPR and are not a comprehensive listing of all possible relevant endpoints. Haematotoxicity, immunotoxicity, neurotoxicity, liver and kidney toxicity, endocrine effects as well as developmental effects are taken into account as acute toxic alerts, relevant for the consideration of ARfDs for pesticides. The general biological background and the data available through standard toxicological testing for regulatory purposes, interpretation of the data, conclusions and recommendations for future improvements are described for each relevant endpoint. The paper also considers a single dose study protocol. This type of study is not intended to be included in routine toxicological testing for regulatory purposes, but rather to guide further testing when the current database indicates the necessity for an ARfD but does not allow a reliable derivation of the value.