1. The effects of acetylcholine and methylfurmetide on isolated guinea-pigs heart atria in the presence or absence of O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate (EDMM) were investigated. The influence of three cholinesterase reactivators on the heart atria pretreated with EDMM has been studied. 2. In the presence of EDMM, the negative inotropic effect of acetylcholine on the isolated heart atria was not significantly increased. This effect of methylfurmetide on heart atria was significantly decreased in the presence of EDMM. 3. EDMM alone caused negative inotropic and negative chronotropic effects depending on its concentration. These pharmacological effects were accompanied with inhibition of acetylcholinesterase activity in the heart muscle. 4. Addition of cholinesterase reactivators normalized the inotropic response of the isolated guinea-pig heart atria altered by EDMM and also increased the acetylcholinesterase activity in the heart.