Cholinesterase activity in the brain, RBC and plasma of Swiss mice was determined following different routes of administration of methamidophos. Continuous feeding with the insecticide caused a progressive inhibition of both plasma- and erythrocyte enzymes. The effect of methamidophos was more pronounced when applied in diet than when administered dermally or intraperitoneally. Following a single injection (i.p.) of methamidophos, the brain enzyme showed maximum inhibition 24 hr following treatment. At the appearance of tremors, the plasma and RBC-enzymes showed considerable inhibition, the former being more inhibited. The plasma enzyme appears to be the most sensitive enzyme and may be taken as a suitable index for exposure to methamidophos.