Two microelectrodes were inserted into the identified ganglion cells of Aplysia and acetylcholine (ACh)-induced responses of depolarizing type (D-) and hyperpolarizing type (H-) were evaluated by the increase in membrane conductance of individual neurons. Various chemicals were mixed in Aplysia Ringer and applied directly to the exposed cells. A. Effects of different sulfhydryl-reagents on the ACh- induced responses of both D- and H-types: We found that mercurials are potent inhibitors the H-type receptor activity. Particularly, Mersalyl is highly selective to the H-type without depressing D-type receptor activity. PMB (p-Hydroxymercuribenzoate) and HgCl2 greatly depress the H-type but slightly the D-type receptor activity. Effects of mono- iodoacetamide, 5-5'Dithiobis-2-nitrobenzoate and N-Ethylmaleimide were not remarkable, however. B. Effects of dimethylsulfoxide (DMSO) on the cholinergic transmission of D. and H-tyeps: We found that 8.3% DMSO is a mild depolarizer. This depolarization is associated with a decrease in membrane permeability toward K ion. The spike duration increases and the after-hyperpolarization decreases when exposed to 8.3% DMSO. DMSO reversibly supresses the ACh-esterase as well as ACh-receptor activities, although the effect on the former is faster. D-type receptor activity is more susceptible to DMSO than that of H-type. C. Effects of lysergic acid diethylamide (LSD-25) on the postsynaptic responses to ACh, serotonine (5-HT), gamma-aminobutyric acid (GABA) and dopamine: Neither response to ACh, 5-HT, and GABA was significantly affected by 1 min. exposure to 0.1 micromolar LSD. Dopamine-induced responses of the hyperpolarizing type were greatly depressed by 1 min. exposure to 1 micron M LSD. The significant depression was observable after 30 sec. exposure to 0.1 micron M LSD. Extremely high sensitivity, gradual onset of depression and long lasting effect resembled the clinical features of psychotic symptoms.