1. In vitro detoxification of the organophosphate (OP) insecticides paraoxon, chlorpyrifos-oxon and malaoxon has been investigated in human serum. 2. Specific A-esterase activity to each OP substrate was measured in the serum of 100 individuals using established spectrophotometric methods for paraoxonase and chlorpyrifos-oxonase and a novel assay for malaoxonase activity. 3. Dose-effect inhibition of serum cholinesterase by the three OPs was measured in pooled human serum. Inhibition of calcium dependent A-esterases by addition of EDTA resulted in increased inhibition of cholinesterase at a given OP concentration. 4. Data from both the direct spectrophotometric measurement of A-esterase activity and inhibition of serum cholinesterase in the presence and absence of A-esterase activity indicated that human serum A-esterase catalysed detoxification of chlorpyrifos-oxon> paraoxon> malaoxon. Our data also confirms the wide variation in potency to inhibit cholinesterase between the three OPs. 5. Malaoxonase activity in human serum does not appear to be polymorphic, however, there is large inter-individual variation as has been previously found for other A-esterases. 6. This study has demonstrated two approaches to investigate the inter-individual variation towards specific OPs and the relative ability of human serum A-esterase to detoxify specific OP compounds.