Calcium-dependent and EDTA-resistant hydrolyses of R and S isomers of O-hexyl O-2,5-dicholorophenyl phosphoramidate (HDCP) were observed in serum and subcellular fractions of liver, kidney and brain from hen, rat and rabbit. In serum, the Ca 2+-dependent hydrolysis was much higher in rabbit than in other species. Liver showed a higher activity than kidney and brain. The S-HDCP isomer was hydrolysed to a higher extent than the other isomer. The fact that this stereospecificity favours the S-isomer is more clearly observed in rabbit serum, and in rat and rabbit liver particulate fractions. In such tissues and species, the EDTA-resistant hydrolysis was not stereospecific. Soluble fractions of rat brain and of hen liver, kidney and brain, showed a lower total activity but with a higher proportion of EDTA-resistant activity and a higher hydrolysis of the R-HDCP isomer. The Ca 2+-dependent stereoselective biodegradation of S-HDCP is dominant in the most active tissues in rabbit and rat. It can therefore be concluded that S-HDCP would be biodegraded faster than R-HDCP. Furthermore, R-HDCP is the isomer that will remain at a higher proportion to be available for interaction with the target of neurotoxicity.