The kinetics of inhibition of horse serum cholinesterase (EC 3.1.1.8) by six trialkylphosphorothiolates was studies (25 degrees C, pH 7.4). The compounds were : OOS-trimethylphosphorothiolate (OOS-Me), OSS-trimethylphosphorodithiolate (OSS-Me), SSS-trimethylphosphorotrithiolate (SSS-Me) and their corresponding ethyl analogues (OOS-Et, OSS-Et, SSS-Et). The second order rate constants of inhibition ranged from 7.2 to 2128 mol-1 1 min-1, of inhibition ranged from 7.2 to 2128 mol-1 1 min-1, and the enzyme/inhibitor dissociation constants from 0.079 to 1.5 mM. The ethyl esters were better inhibitors than their methyl analogues and the OSS-compounds were better inhibitors than the OOS- or SSS-compounds. The same structure-activity relationship is known to hold for the reaction of the compounds with acetylcholinesterase (EC 3.1.1.7).