Summary The quantities of active cholin-esterase inhibitors which accumulated when Malathion, Parathion and Guthion were incubated with liver slices from 2 mammalian, 2 avian and 4 piscine species were measured. The capacities of liver homogenates from these 3 classes of animals to inactivate the oxygen analogues of these compounds were also compared. The relative capacities of liver slices from various species to produce and accumulate cholinesterase inhibitors varied depending upon the thiophosphate studied. Fish livers had considerably less capacity than mammalian and avian livers to inactivate the oxygen analogues of Parathion and Malathion, but the destruction of the anticholinesterase activity of Gutoxon by liver homogenates did not differ appreciably among the 3 classes. The greater susceptibility of sunfish than mice to poisoning by Malathion or Malaoxon correlated well with what would be predicted from the liver metabolism studies. Toxicity-metabolism correlations were less obvious for Guthion and Gutoxon, and the lesser susceptibility of sun-fish than mice to poisoning by Parathion and Paraoxon was opposite to what would be expected from liver metabolism data,