The overall goal of this research project was to investigate the mechanism(s) of acute toxicity of formamidine pesticides in mammals using chlordimeform (N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine) and its metabolites as the primary model compounds. The role of biotransformations, particularly N-demethylation reactions, in generating potentially toxic metabolites was also studied. By comparing the effects of hepatic microsomal mixed function oxidase inducers and inhibitors administered in vivo on the toxicity, metabolism, and distribution of metabolites in mouse tissues, it was concluded that although N-demethylation products are innately more toxic than chlordimeform, they are also less stable, and the best correlation of toxicity was obtained with the total level of formamidines in the brain, rather than with the level of any individual metabolite. In a series of studies with dogs, rabbits, and cats, the cause of death was found to be cardiovascular collapse accompanied by respiratory arrest. Cardiovascular collapse resulted primarily from a peripheral local anesthetic-like effect of chlordimeform. Monoamine oxidase inhibition was not a major factor in lethality. Respiratory arrest was central in origin. Several other central effects of the formamidines were described, some of which may be local anesthetic actions, and a behavioral profile for chlordimeform poisoning in the rat was developed. The effectiveness of various drug treatments as potential therapeutic aids for formamidine intoxication were studied. Formamidines also have aspirin-like actions due to an inability to inhibit prostaglandin synthesis.