The side effects of four phosphorylated cholinesterase reactivators (oximes): contrathion, TMB4, toxogonine and 1574 SEBC on membrane properties and synaptic transmission of Aplysia central neurons were investigated. Applied in the bath at 10(-3) mol X 1(-1) to 10(-2) mol X 1(-1) concentrations, all these oximes had a depressive action on cholinergic transmission exerting a curare-like effect on the postsynaptic receptors. In addition, Toxogonin and TMB4 affected the presynaptic voltage dependent sodium conductance. None of these oximes interfered with the voltage dependent potassium or calcium conductances. The oximes had a transient facilitatory action on amplitude of the response to ionophoretically applied acetylcholine (ACh) on H-type ACh receptors, but not on cells with D-type ACh receptors. The K+ dependent response to ACh injection on pleural ganglion cells was selectively blocked by 5 X 10(-6) mol X 1(-1) contrathion. All oximes at 10(-2) mol X 1(-1) to 10(-3) mol X 1(-1) similarly depressed serotonin receptors in buccal ganglion cells. All the effects of oximes were reversible by washing. It was concluded that oximes can act as 1) inhibitors of Na+ conductance, 2) antagonists for various synaptic receptors, 3) reversible inhibitors of acetylcholinesterase.