SummaryThe activity of cholinesterase was measured in brain cortex, basal ganglia, hippocampus, thalamus, colliculi, cerebellum, medulla, hypothalamus, spinal cord, gastrornemius muscle, adrenal gland and retina at various times after treatment of rats with diisopropyl fluorophosphate alone or together with 1,3‐bis(4‐hydroxyiminomethylpyridinium) propane dibromide (C434)2. After injection of 1 mg. diisopropyl fluorophosphate/kg. body weight intramuscularly in the; leg the eholinesterase activity of neural tissue was decreased to 30–40% of control values and it increased to 70–100% of control values in 25 days. In each case the rate of increase of activity with time decreased throughout this period, and was not changed significantly by concurrent treatment with C434. The proportional rate of increase in the cerebellum was significantly greater than that in other neural tissue.The decrease in cholinesterasc activity of leg muscle injected with diisopropyl fluorophosphate was less marked in animals treated with C434. The activity in adrenals returned to control values within 5 days and was 100–120% of control values for 5–10 days; these effects were not altered by treatment with C434.Rats injected initially with 1·0 mg. and subsequently on every third day with 0·5 mg./kg. body weight of diisopropyl fluorophosphate, with or without C434, for periods up to 62 days showed no behavioural abnormalities or evidence of toxic effects, although the cholinesterase activity of regions of the brain was 20–40% of control values. In chronic treated animals C434 did not significantly alter muscle cholinesterase activity.