At Aplysia H- and D-type cholinergic neuro-neuronal synapses, application of high concentrations of detergents (Triton X-100 and sodium deoxycholate) depressed synaptic transmission and the postsynaptic response to ionophoretic application of acetylcholine (ACh) or carbachol. However, when very low concentrations of detergents (of the order of 10(-9) M for sodium deoxycholate) were used, the nerve-evoked response as well as the ACh and carbachol ionophoretic responses were facilitated (by at least 200%), but only in H-type cells. This facilitation was similar to that previously observed in the same receptor type when acetylcholinesterase (AChE) was inhibited by various organophosphate or carbamate acetylcholinesterase inhibitors (AChEIs)3. Indeed, the effects of AChEI and detergents were not cumulative. We propose that on H-type synapses detergents may perturb a hypothetical molecular interaction between AChE and the acetylcholine receptor (AChR) by which AChE modulates the ability of the AChR to be activated by ACh or carbachol.