To establish the dose dependency of phospholipase A2 (PLA2) inhibition by the organophosphorus compound (OPC) paraoxon (POX), human platelet membranes were incubated after Ca2+ removal (to inactivate the PLA2) with 0.3, 1 and 3 microg ml(-1) POX for 5, 30 and 60 min each. The PLA2 activity (pmol mg[-1] protein min[-1]) was measured after subsequent enzyme reactivation. The PLA2 activity in native platelets was considered to be 100%; all other measured values are expressed as a percentage thereof. Data were analysed with the Mann-Whitney Wilcoxon rank order test and ANOVA. Statistical significance was assumed for P < or = 0.01. Paraoxon inhibited in a dose-dependent manner the PLA2 activity. Different incubation times of the inactive PLA2 with POX did not have any additional effect on the activity reduction after activation. At the tested POX concentrations the PLA2 activity was 42 +/- 5.4%, 29 +/- 3.4% and 15 +/- 6.6%, respectively. The corresponding butyrylcholine esterase (BChE) activities were <<1% of the baseline activity. Phospholipase A2 is less sensitive to POX inhibition than BChE and, at clinically achievable POX concentrations, shows a clear dose dependency. Further work is needed to elucidate the exact mechanism and time dependency of the phenomenon.