Micromolar concentrations of methylmercury and several organic mercury fungicides were found to block binding of [3H]acetylcholine (ACh) to the ACh-receptor of the electric organ of the electric ray, Torpedo ocellata. The same compounds had little or no effect on the catalytic activity of ACh-esterase of the same tissue. [14C]Methyl-mercury bound to the purified ACh-receptor with high affinity (Kd=7micrometer) and there were 6.5 +/- 0.5 binding sites for each ACh-binding site. Binding of methylmercury was highly cooperative with a Hill coefficient of 2.6. This binding was irreversible by redialysis in methylmercury - free medium, however, the bound [14C]methylmercury was easily displaced from the receptor protein with micrometer concentrations of BAL or penicillamine. Methylmercury also blocked binding of [3H] nicotine and [3H]pilocarpine to the nicotinic and muscarinic ACh-receptors of the rat brain, respectively. The data suggest that the ACh-receptor may be a target for methylmercury and other organic mercury compounds.