In vitro intracellular recording techniques were used on an excitatory neuromuscular junction of a walking-limb stretcher muscle of the lobster in order to define the synaptic pharmacology of delta-9-tetrahydrocannabinol (THC), 11-hydroxy-THC and cannabidiol. Delta-9-tetrahydrocannabinol and 11-hydroxy-THC, in relatively small concentrations, increased the amplitude of the excitatory junctional potential and the mean quantum content of a muscle fiber, whereas larger concentrations produced depression. In contrast, cannabidiol reduced the excitatory junctional potential and the mean quantum content. All three cannabinoids, however, depressed the amplitude of the spontaneous miniature junctional potential. The changes in mean quantum content point to a presynaptic site of action for the drug, while the reduction of the amplitude of the miniature junctional potential presumes a postsynaptic site. Such findings suggest synaptic mechanisms and sites of action for the central excitatory and depressant properties of the cannabinoids.