The saccule is one of the vestibular sensory organs of the inner ear. It detects head movements and provides information to maintain balance and orient in space. Despite its critical role, very little is known about its neurotransmission and regulation. Multiple disease entities and medications affect balance, which is why information on neurotransmission in the vestibular end organs including the saccule could have important pharmacological implications. To the best of our knowledge, this is the first paper to describe immunohistochemical expression of a large panel of neurotransmitters and receptors in the human saccule. Saccular tissue was sampled freshly during surgery. Based partly on previous findings in non-humans and partly on potential biological relevance, the neurotransmitters cholecystokinin, dopamine, GABA, glutamate, histamine and serotonin as well as receptors for these were selected for the tested panel. The neuroepithelium expressed glutamate receptor 1 (GluR1), metabotropic glutamate receptor (mGluR), GABA A receptor α (GABA_ARα), GABA B receptor 2 and cholecystokinin receptor B (CCKBR), whereas L-glutamate, GluR1, CCKBR, GABA_ARα, dopamine and serotonin receptor 1D were expressed in the subepithelial stroma. The non-sensory epithelium expressed GluR1, mGluR, histamine receptor 3, CCKAR and dopamine transporter. These findings provide a basis for pharmacological research and potential drug development.