The concept that each nerve cell makes and releases only one nerve transmitter (widely known as Dale's Principle) has been re-examined. Experiments suggesting that some nerve cells store and release more than one transmitter have been reviewed. Developmental and evolutionary factors are considered. Conceptual and experimental difficulties in investigating this problem are discussed. It is suggested that the term 'transmitter' should be applied to any substance that is synthesised and stored in nerve cells, is released during nerve activity and whose interaction with specific receptors on the postsynaptic membrane leads to changes in postsynaptic activity. Expressed in this way, it seems likely that while many nerves do have only one transmitter, others in some species, during development or during hormone-dependent cycles, employ multiple transmitters.